(2-imidazolin-2-yl) fused heteropyridine compounds, intermediates for the preparation of and use of said compounds as herbicidal agents

ABSTRACT

There are provided novel (2-imidazolin-2-yl) fused heteropyridine compounds, and intermediate compounds for the preparation thereof, and a method for controlling a wide variety of annual and perennial plant species therewith.

This is a divisional of copending application Ser. No. 08/123,827 filedon Sept. 20, 1993, which is a divisional of application Ser. No.07/465,569 filed Jan. 16, 1990, now U.S. Pat. 5,252,538, which is acontinuation of U.S. Ser. 07/178,408 filed Apr. 6, 1988, now abandoned,which is a continuation of U.S. Ser. No. 06/876,599 filed Jun. 20, 1986,now abandoned, which is a continuation-in-part of U.S. Ser. No.06/808,578 filed Dec. 13, 1985, now abandoned and U.S. Ser. No. 612,531filed May 21, 1984 now U.S. Pat. 5,129,454.

BACKGROUND OF THE INVENTION

Novel herbicidal imidazolinyl benzoic acids, esters and salts, theirpreparation and use are disclosed in U.S. Pat. No. 4,188,487, and U.S.Pat. No. 4,297,128 and pending application for U.S. patent applicationSer. Nos. 579,224, 631,283 and 629,296, while various novel pyridine andquinoline imidazolinone compounds are described in pending applicationsfor U.S. patent application Ser. Nos. 382,041 and 616,747. PendingApplication for U.S. patent application Ser. No. 676,133, filed Nov. 29,1984, describes herbicidal (2-imidazolin-2-yl)-thieno-and furo[2,3-b]and(3,2-b]pyridines, their preparation and use.

It is an object of this invention to provide the novel herbicidal(2-imidazol in-2-yl) fused heteropyridine compounds of the generalformula: ##STR1## wherein D-E together with the two aromatic carbonatoms to which they are joined, represents a five or six membered ringcontaining from one to three heteroatoms, which may contain a variety ofsubstituents: a method for their preparation; and the use of saidcompounds for controlling a wide variety of annual and perennial plantspecies therewith.

SUMMARY OF THE INVENTION

The invention is novel herbicidal (2-imidazolin-2-yl) fusedheteropyridine compounds having the structures I to XXIV below ##STR2##

wherein A is COOR₈, CHO, CH₂ OH, COCO₂ OH, CONH₂, CH₂ CO₂ OH, CONHOH or##STR3##

R_(C) and R_(D) are each hydrogen or C₁ -C₄ alkyl;

R₈ is hydrogen, C₁ -C₄ alkyl, which may be interrupted by O or S, or isoptionally substituted with C₁ -C₄ alkoxy, halogen, hydroxy, C₃ -C₆cycloalkyl, benzyloxy, furyl, phenyl, furfuryl, halophenyl, C₁ -C₄alkylphenyl, C₁ -C₄ alkoxyphenyl, nitrophenyl, carboxyl, C₁ -C₄alkoxycarbonyl, cyano or C₁ -C₄ trialkylammonium; C₃ -C₆ alkenyl,optionally substituted with one or two C₁ -C₃ alkoxy, phenyl or halogengroups; C₃ -C₆ cycloalkyl, optionally substituted with one or two C₁ -C₃alkyl groups; C₃ -C₁₀ alkynyl, optionally substituted with phenyl,halogen, loweralkoxy; or a cation;

B is H, COR₉ or SO₂ R₁₀, R₉ is C₁ -C₁₁ alkyl, chloromethyl, C₁ -C₄loweralkoxyl or phenyl optionally substituted with one chloro, onenitro, one methyl, or one methoxy group; R₁₀ is C₁ -C₅ alkyl, phenyl, orphenyl optionally substituted with one methyl, halogen, nitro, or C₁ -C₄alkoxy;

R₁ is C₁ -C₄ alkyl;

R₂ is C₁ -C₄ alkyl or C₃ -C₆ cycloalkyl; and when taken together withthe carbon to which they are attached, R₁ and R₂ may represent C₃ -C₆cycloalkyl, optionally substituted with methyl;

--- represents a single or double bond;

W is O or S;

X₁, X₂, X₃ and X₄ are any combination of from zero to three CR₄ or CR₅R₆ ; from zero to three N or NR₃ and from zero to two O or S; Y₁ and Y₂are N or CR₄ and are the same or different; Z₁ and Z₂ are O, S, NR₃ orCR₅ R₆, and are the same or different, with the proviso that at leastone of X₁₋₄, Y₁₋₂, or Z₁₋₂ is a heteroatom in each of Structure I-XXIVcompounds;

R₃ is C₁ -C₄ alkyl, which may be optionally substituted with phenyl orone or more halogens; C₃ -C₆ alkenyl, optionally substituted with phenylor one or more halogens; C₃ -C₆ alkynyl, optionally substituted withphenyl or halogen; C₁ -C₄ alkoxy, optionally substituted with phenyl orone or more halogens; C₃ -C₆ alkenyloxy, optionally substituted withphenyl or one or more halogens; C₃ -C₆ alkynyloxy optionally substitutedwith halogen or phenyl or C₂ -C₆ alkanoyloxy, optionally substitutedwith halogen or phenyl;

R₄ is hydrogen, halogen, C₁ -C₆ alkyl; C₁ -C₄ alkoxy; C₂ -C₆alkanoyloxy; C₁ -C₄ alkylthio; phenoxy; C₁ -C₄ haloalkyl; C₁ -C₄haloalkoxy; nitro, C₁ -C₄ alkoxycarbonyl; C₁ -C₄ dialkylamino; C₁ -C₄alkylsulfonyl or phenyl, optionally substituted with one or two C₁ -C₄alkyl, C₁ -C₄ alkoxy, halogen or haloalkyl;

R₅ and R₆ are each hydrogen, C₁ -C₄ alkyl; C₁ -C₄ alkoxy, C₁ -C₄haloalkoxy; nitro, C₁ -C₄ alkylsulfonyl or phenyl optionally substitutedwith one or two C₁ -C₄ alkyl, C₁ -C₄ alkoxy, halogen or haloalkyl: orany combination of these groups except when R₅ and R₆ are the samegroup, they are either both hydrogen or both C₁ -C₄ alkyl; and whentaken together, R₅ and R₆ may form a ring in which R₅ R₆ are representedby the structure --(CH₂)_(n) -- where n is an integer of ₄ or 5, or whentaken together, R₅ and R₆ may form a group =O or --NR₇ wherein R₇ isphenyl, C₁ -C₄ alkyl, C₁ -C₄ alkoxy or C₁ -C₄ alkylamino;

R₃, R₄, R₅ or R₆ when present on adjacent positions may, along with theatoms to which they are attached, form a ring and such R₃ -R₆ pairs canbe represented by the structure --(CH₂)_(m) -- or --(CH)_(m) -- where mis an integer of 3 or 4;

with the provisos that in structures II, VI, X, XIV, XVIII and XXII,when X₁ is O or S, at least one of X₂ and X₄ may not be CR₄ or CR₅ R₆ ;when X₄ is O or S, at least one of X₁ and X₂ may not be CR₄ or CR₅ R₆ ;in structures IV, VIII, XII, XVI, XX and XXIV when Z₁ is O, Y₁ and Y₂may not be CR₄ ;

--- represents a single bond between:

X₁ and X₂ when either X₁ or X₂ is S, O, NR₃ or CR₅ R₆ ;

X₂ and X₃ in structures I, V, IX, XIII, XVII and XXI, when either X₂ orX₃ is O, S, NR₃ or CR₅ R₆ ;

X₃ and X₄ in structures I, V, IX, XIII, XVII and XXI, when either X₃ orX₄ is O, S, NR₃ or CR₅ R₆ ;

X₂ and X₄ in structures II, VI, X, XIV, XVIII and XXII. when either X₂or X₄ is O, S, NR₃ or CR₅ R₆ ;

when one of X₁₋₄ is oxygen, the X₁₋₄ to which it is attached is N, NR₃,CR₄ or CR₅ R₆ ;

and in structures III, VII, XI, XV, XIX and XXIII, when one of Z₁₋₂ isoxygen, the Z₁₋₂ to which it is attached is NR₃ or CR₅ R₄ ;

when B is COR₉ or SO₂ R₁₀ and R₈ is hydrogen, then -- represents anaromatic bond, R₃ is C₁ -C₄ alkyl and R₄, R₅ and R₆ may not be halogen.

Structure I-XXIV compounds also include tautomers thereof,agriculturally acceptable acid addition salts and other additioncompounds thereof, the N-oxides thereof when A is COORS; and when R₁ andR₂ are not the same, the optical isomers thereof.

This invention also includes novel herbicidal compounds of the formula##STR4## wherein R₁ is C₁ -C₄ alkyl; R₂ is C₁ -C₄ alkyl or C₃ -C₆,cycloalkyl; and when R₁ and R₂ are taken together with the carbon towhich they are attached they may represent C₃ -C₆ cycloalkyl optionallysubstituted with methyl; A is COOR₈, CHO, CH₂ OH, COCO₂ OH, CONHCH₂ OH,CONHOH, or ##STR5## R₈ is hydrogen, C₁ -C₁₂ alkyl optionally substitutedwith one of the following groups: C₁ -C₃ alkoxy, halogen, hydroxy, C₃-C₆ cycloalkyl, benzyloxy, furyl, phenyl, furfuryl, halophenyl,loweralkylphenyl, loweralkoxyphenyl, nitrophenyl, carboxyl,loweralkoxycarbonyl, cyano, C₁ -C₄ alkylthio or triloweralkylammonium,in addition the alkyl chain may be interrupted by one or more O or S; C₃-C₆ alkenyl optionally substituted with one of the following groups: C₁-C₃ alkoxy, phenyl, halogen or with two C₁ -C₃ alkoxy groups or twohalogen groups: C₃ -C₆ cycloalkyl optionally substituted with one or twoC₁ -C₃ alkyl groups; C₃ -C₁₀ alkynyl optionally substituted with phenyl,halogen or CH₂ OH; or a cation selected from the group consisting ofalkali metals, alkaline earth metals, (Ca, Ba) and manganese. copper,iron, ammonium and organic ammonium; R_(C) and R_(D) are H, or CH₃ ; Bis H, COR₉ or SO₂ R₁₀, provided that when B is COR₉ or SO₂ R₁₂, and A isCOOR₈, R₈ cannot be hydrogen or a salt-forming cation; R₁₁ is C₁ -C₁₁alkyl, chloromethyl or phenyl optionally substituted with one chloro,one nitro, one methyl, or one methoxy group; R₁₀ is C₁ -C₅ alkyl orphenyl optionally substituted with one methyl group, chloro or nitro; Wis O or S; X is O, S, or --S=O; Y and Y', Z and Z' are hydrogen,halogen, C₁ -C₆ alkyl, C₁ -C₄ hydroxyloweralkyl, C₁ -C₆ alkoxy, C₁ -C₆acyloxy, benzoyloxy optionally substituted with one or two C₁ -C₄ alkyl,C₁ -C₄ alkoxy, halogen; C₁ -C₄ alkylthio, phenoxy, C₁ -C₄ haloalkyl, C₁-C₄ haloalkoxy, nitro, cyano, C₁ -C.sub. 4 alkylamino, C₁ -C₄dialkylamino, C₁ -C₄ alkylsulfonyl or phenyl optionally substituted withone or two C₁ -C₄ alkyl, C₁ -C₄ alkoxy, halogen, or any combination oftwo of these groups and wherein Y and Z are the same group provided thatY and Z are H, halogen, alkyl or alkoxy, and when Y and Y' or Z and Z'are the same group they are hydrogen or alkyl: and the pyridine N-oxidesthereof, when W is O or S and A is COOR₈ ; and when R₁ and R₂ are notthe same, the optical isomers thereof, and, except when R₈ is asalt-forming cation, the acid addition salts thereof.

Ring systems formed by X₁₋₄, Z₁₋₂ and Y₁₋₂ and encompassed by thisinvention include six-membered rings containing:

one heteroatom, where one of X₁₋₄, Y₁₋₂ or Z₁₋₂ is O, S, N, or NR₃.Examples of these are pyrano-. thiopyrano-, tetrahydropyrido-, pyrido-,dihydropyrano-. dibydropyrido-, and dibydrotbiopyrano-pyridines.

two heteroatoms, where two of X₁₋₄, Y₁₋₂ and Z₁₋₂ are O, S, N or NR₃,examples of which are dioxino-, dithiino-, oxazino-, oxathiino,pyrazino-, thiazino-, pyridazino-and pyrimidino-pyridines; and the di-and tetrahydro derivatives of these ring systems;

three heteroatoms, where three of X₁₋₄, Y₁₋₂ and Z₁₋₂ are N or NR₃.Examples of these are triazino-, dihydrotriazino- andtetrahydrotriazino-pyridines.

Five-membered ring systems include five-membered rings containing:

one heteroatom, where one of X₁₋₄, Y₁₋₂ or Z₁₋₂ is N or NR₃, such as thepyrrolopyridines and the dihydropyrrolopyridines;

two heteroatoms, where two of X₁₋₄, Y₁₋₂ and Z₁₋₂ are each O, S, N orNR₃ such as dioxolo-, dithiolo-. imidazo, imidazolino-, pyrazolo-,pyrazolino-, oxazolo-. oxazolino-, isoxazolo-, isoxazolino-, thiazolo-,thiazolino-, isothiazolo-, isotbiazolino-, and oxathiolo-pyridines;

three heteroatoms where three of X₁₋₄, Y₁₋₂ and Z₁₋₂ are N, NR₃, O or Ssuch as thiadiazolo-, thiadiazolino-, oxadiazolo-, oxadiazolino-,triazolino- or triazolopyridines.

Preferred heteropyridine ring systems of structure I--XXIV compounds arepyranopyridines, pyrrolopyridines, pyrazolopyridines, imidazopyridines,oxazolopyridines, isoxazolopyridines, dithiolopyridines,dioxolopyridines, dioxinopyridines, dithiinopyridines, pyridopyridines(naphthyridines) , thinoyranopyridines, oxazinopyridines,oxathiinopyridines and thiazinopyridines; and the dihydro and tetrahydroderivatives of these ring systems:

wherein R₁ is methyl or ethyl, R₂ is ethyl, propyl or isopropyl, andwhen R₁ and R₂ are taken together, they represent a cyclohexyl ring,optionally substituted with methyl; R₃ is C₁ -C₃ alkyl, C₁ -C₄ alkoxy,allyloxy, CF₃ O--, CF₂ HO-- or CF₃ ;

R₄ R₅ and R₆ are each hydrogen, chlorine, bromine, C₁ -C₃ alkyl, C₁ -C₃alkoxy, C₁ -C₃ alkylthio, C₁ -C₂ dialkylamino, or when R₅ and R₄ aretaken together form the doubly bonded oxygen of a carbonyl group;

A is COOR₈ where R₈ is H, C₁ -C₄ alkyl, which may be interrupted by O orS and is optionally substituted with furyl, propynyl, phenyl orhalophenyl; C₁ -C₄ alkylphenyl, C₁ -C₄ alkoxyphenyl or nitrophenyl, or acation;

B is H, acetyl, C₁ -C₄ alkylsulfonyl or phenylsulfonyl optionallysubstituted with C₁ -C₄ loweralkyl, nitro, chloro or C₁ -C₄ loweralkoxy;W is O or S.

A more preferred group of structures are those of I-XXIV where only oneor two of X₁₋₄, Y₁₋₂ and Z₁₋₂ are each O, S, N, or NR₃ ;

A is COOR₈ where R₈ is hydrogen, methyl, ethyl, methoxyethyl,ethoxyethyl, methylthiomethyl, methylthioethyl, propargyl,phenyl-substituted alkyl, furfuryl, or a sodium, calcium, lithium,potassium, magnesium, ammonium, or organic ammonium cation;

B is H, benzoyl acetyl, methanesulfonyl or p-toluenesulfonyl;

R₁ is methyl and R₂ is isopropyl;

R₃ is methyl, ethyl, methoxy, ethoxy and allyloxy;

R₄, R₅ and R₆ are each methyl, ethyl, chloro, bromo, hydrogen, methoxyand ethoxyl, or R₅ R₆, when taken together are =O;

and W is O.

A more preferred group of structures are those of formula I-XXIV inwhich the heterocyclic rings are pyrano-, thiopyrano, dioxino, pyrrolo,pyrazolo, and dioxolopyridines.

wherein R₁ is methyl, R₂ is isopropyl, R₃ is CH₃ or OCH₃, B is hydrogen,W is oxygen, A is COOH and the agriculturally acceptable salts andesters of these acids.

A most preferred group of structures are those of formula I-IV in whichthe heterocyclic rings are pyrano-, thiopyrano, dioxino, pyrrolo,pyrazolo and dioxolopyridines wherein R₁ is methyl, R₂ is isopropyl, R₃is CH₃ or OCH₃, B is hydrogen, W is oxygen, A is COOH and theagriculturally acceptable salts and esters of these acids.

In formulas I to IV and XVIII to XX above, preferred cations includealkali metals such as: sodium, potassium and lithium, but sodium isgenerally preferred: or organic ammonium which is defined as a groupconsisting of a positively charged nitrogen atom joined to from one tofour aliphatic groups, each containing from one to 20 carbon atoms.Among the organic ammonium groups which are illustrative for thepreparation of the aliphatic ammonium salt of the formulas I to IV andXVIII to XX--imidazolinyl fused heteropyridine acids herein are:monoalkylammonium, dialkylammonium, trialkylammonium,tetraalkylammonium, monoalkenylammonium, dialkenylammonium,trialkenylammonium, monoalkynylammonium, dialkynylammonium,trialkynylammonium, monoalkanolammonium, dialkanolammonium,trialkanolammonium, C₅ -C₆ -cycloalkylammonium, piperidinium,morpholinium, pyrrolidinium, benzylammonium and equivalents thereof.

In general, and for convenience, the compounds of the invention may berepresented by structures XXV-XXX below ##STR6## wherein D-E togetherwith the two aromatic carbons to which they are joined, represents afive or six membered ring as described in formulas I to XXIV above.

The compounds of the present invention may conveniently be prepared fromthe appropriately substituted fused heteropyridinedicarboxylic acids andesters, which may be represented in general by the formula ##STR7##wherein D-E forms part of a five-or six-membered ring as previouslydescribed for formulas I-XXIV above.

Thus, diesters of the above general formula XXXI may be hydrolyzed tothe corresponding heteropyridine-2,3-carboxylic acids of formula XXXIaand by reaction thereof with a strong base such as potassium hydroxideor sodium hydroxide. Acid anhydrides of formula XXXII may then beprepared by treatment of the formula XXXIa heteropyridinedicarboxylicacids with, for example, acetic anhydride. Reaction of formula XXXIIanhydrides with an appropriately substituted aminocarboxamide oraminothiocarboxamide depicted by formula XXXIII yields carbamoylheteropyridine acids of formula XXX. Treatment of the thus-formedformula XXX carbamoyl heteropyridine acids with about two to ten molarequivalents of aqueous or aqueous alcoholic sodium or potassiumhydroxide, preferably under a blanket of inert gas such as nitrogen,cooling and acidifying to pH 2 to ₄ with a strong mineral acid such ashydrochloric acid or sulfuric acid gives herbicidally effective formulaXXIXa (4,4-disubstituted-5-oxo-(or thioxo)-2-imidazolin-2-yl) fusedheteropyridine nicotinic acids, as illustrated in Flow Diagram I below.##STR8##

General formula XXIXb (2-imidazolin-2-yl) fused heteropyridine esters,wherein R₈ represents a substituent other than hydrogen or asalt-forming cation, can be prepared by reacting a novel fusedimidazopyrrolo-heteropyridinedione, represented by the general formulaXXV or XXVI, hereinbelow, in Flow Diagram II, with an appropriatealcohol and corresponding alkali metal alkoxide at a temperature rangingbetween about 20° C. and about 50° C.

Formula XXVI novel fused imidazopyrroloheteropyridinediones mayconveniently be prepared from formula XXIXa acids by treatment with oneequivalent of dicyclohexylcarbodiimide in an inert solvent such asmethylene chloride as illustrated in Flow Diagram II below.

Formula XXV imidazopyrroloheteropyridinediones may be prepared fromformula XXIXa compounds by treatment with one to three equivalents ofacetic anhydride in pyridine.

Treatment of formula XXIXb esters with an acylating agent such as acetylchloride or acetic anhydride or a sulfonating agent such asp-toluenesulfonyl chloride in an inert solvent such as tetrahydrofurangives the formula XXIXb esters where B is other than hydrogen as definedabove. The compounds of formula XXIXd are prepared by selective cleavageof the benzyl esters of formula XXIXc with hydrogen and a palladiumcatalyst.

Reduction of formula XXIXb esters with, for instance, sodiumcyanoborohydride, provides the dihydroimidazolinone esters of formulaXXVIII which can be hydrolyzed in base to the corresponding acidcompounds of formula XXVIIIa. An alternate synthesis of formula XXVIIIcompounds is by treatment of formula XXXIV compounds with about oneequivalent of an amino amide compound of formula XXXII and a catalyticamount of p-toluenesulfonic acid in toluene, The ester aldehydecompounds of formula XXXIV may be prepared by reduction of the diesterswith diisobutyl aluminum hydride, The acid compounds of formula XXVIIIamay be treated with acetic anhydride in pyridine to give the dihydroimidazopyrroloheteropyridine diones of formula XXVII. ##STR9##

Many heteropyridine diesters having the general formula XXXI above areeither known in the art, or can be prepared by reacting an amino orenamino heterocycle with oxalacetic esters or acetylenedicarboxylateester.

An amino-substituted heterocycle with at least one unsubstituted orthocarbon may be condensed with oxalacetic acid esters or added toacetylene dicarboxylic esters to give an intermediate enamine. This canthen be treated with one or two equivalents of Viismeier reagent asdescribed in pending application for U.S. Patent of R. Doehner, Ser. No.698,192 filed Feb. 4, 1985 which is incorporated herein by referencethereto, to give the desired diester.

Certain o-amino-heterocyclic aldehydes may be reacted with DMAD oroxalacetic esters in a manner as described by P. Caluwe, Tetrahedron 36,2359 (1980), to give the desired diesters directly.

A novel process of this invention is preparing 5-substituted,6-substituted and 5,6-disubstituted pyridine-2,3-dicarboxylates fromenamines, which may be prepared from heterocyclic rings containing acarbonyl functionality, by allowing them to react with anethoxymethylene compound. The initial product is not isolated but istreated directly with an ammonia source, such as ammonium acetate, togive the diester, which is described more fully after Flow Diagram IIIbelow.

These reactions are illustrated in Flow Diagram III below, wherein D-Etogether with the carbons to which they are joined, represents a five-or six-membered heterocyclic ring; R is methyl or ethyl; R' is hydrogenor CHO: R" and R"' are each hydrogen, C₁ -C₆ alkyl, or taken togetherwith the nitrogen atom to which they are attached may form a five- orsix-membered saturated ring containing a total of, at most, two heretoatoms. ##STR10##

When R" and R"' ₄ H, the above novel enamine reaction is a method forthe preparation of 5-substituted, 6-substituted and 5,6-disubstitutedpyridine 2,3-dicarboxylates of formula XXXIb ##STR11## wherein E ishydrogen, C₁ -C₆ alkyl or phenyl optionally substituted with methyl;

D is hydrogen, C₁ -C₆ alkyl or phenyl optionally substituted with methylor

D and E taken together with the carbons to which they are attached mayform a four to seven membered ring which may contain one oxygen orsulfur, which may be optionally substituted with a methyl group,comprising reacting an enamine of formula XXXIV ##STR12## wherein eachof R₁₁ and R₁₂ is C₁ -C₆ alkyl, or taken together with the nitrogen atomto which they are attached R₁₁ and R₁₂ may form a five or six memberedsaturated ring containing at most two hetero atoms wherein

E is hydrogen, C₁ -C₆ alkyl, or phenyl optionally substituted withmethyl;

D is hydrogen, C₁ -C₆ alkyl, or phenyl optionally substituted withmethyl or D and E taken together with the carbons to which they areattached may form a four to seven membered ring which may contain oneoxygen or sulfur, which may be optionally substituted with a methylgroup with an oxymethylene oxalacetate of formula XXXV ##STR13## whereineach of R₁₃, R₁₄ and R₁₅ is hydrogen or C₁ -C₄ alkyl in an alcoholic,ketonic, halogenated hydrocarbon, hydrocarbon or aromatic solvent oracetonitrile from five minutes to 24 hours at a temperature of from -78°C. to 50° C., and reacting the thus-formed adduct with an ammonia sourcesuch as NH₃ or NH₄ ⁺ X⁻ ;

wherein X is OH, carboxyl or halogen; in a solvent selected fromalcohols, ether-alcohol mixtures, halogenated hydrocarbon-alcoholmixtures, halogenated hydrocarbon-water mixtures or acetic acid for fromthirty minutes to 72 hours, at a temperature of from 0° C. to theboiling point of the solvent system, as illustrated in Flow Diagram IVbelow. ##STR14##

The resulting 5-substituted, 6-substituted and 5,6-disubstitutedpyridine-2,3-dicarboxylates are useful intermediates for the preparationof herbicidal 2-(2-imidazolin-2-yl)pyridine and quinoline acids, estersand salts such as those disclosed in European Patent Application Number81103638.3 filed Dec. 1, 1981, as illustrated in Flow Diagram V below.##STR15## wherein R₁ is C₁ -C₄ alkyl; R₂ is C₁ -C₄ alkyl or C₃ -C₆cycloalkyl; and when R₁ and R₂ are taken together with the carbon towhich they are attached they may represent C₃ -C₆ cycloalkyl optionallysubstituted with methyl; W is O or S; and D and E are as defined forformula XXXIb above.

Additionally the method of the present invention provides a novel methodfor the preparation of 2,3-dihydrofuro[3,2-b]anddibydrothieno[3,2-b]pyridines described in pending Application for U.S.Letters Pat. Ser. No. 500,219, filed Jun. 2, 1983 of Marinus Los, DavidWilliam Ladnet and Barrington Cross, by the reaction ofdiethylethoxymethylene oxalacetate with a mixture of enamines derivedfrom 3-keto-tetrahydrofuran or 3-ketotetrahydrothiophene, followed bytreatment with ammonia or ammonium salts, as illustrated in Flow DiagramVI below. ##STR16## wherein X is O or S; and R₁₁ and R₁₂ are aspreviously described for formula XXXIV above.

Uniquely, as illustrated in Flow Diagram VI above the method of thepresent invention also provides a facile and novel method for thepreparation of novel dihydrofuro[3,4-b] and dihydrothieno[3,4-b]pyridine2,3-dicarboxylates of formula XXXVI ##STR17## wherein R₁₄ and R₁₅ are asdescribed for formula XXXV above; Y and Y' and Z and Z' are hydrogen,halogen, C₁ -C₆ alkyl, C₁ -C₄ hydroxyloweralkyl, C₁ -C₆ alkoxy, C₁ -C₄alkylthio, phenoxy, C₁ -C₄ haloalkyl, C₁ -C₄ haloalkoxy, nitro, cyano,C₁ -C₄ alkylamino, C₁ -C₄ dialkylamino, C₁ -C₄ alkylsulfonyl or phenyloptionally substituted with one or two C₁ -C₄ alkyl, C₁ -C₄ alkoxy,halogen, or any combination of two of these groups and wherein Y and Zare the same group provided that Y and Z are H, halogen, alkyl oralkoxy, and when Y and Y' or Z and Z' are the same group, they arehydrogen or alkyl.

The novel formula XXXVI compounds may in turn be converted by theprocedure illustrated in Flow Diagram V to novel herbicidal5,7-dihydro-2-(.2-imidazolin-2-yl)thieno and furo[3,4-b]pyridinecompounds having the structure XXXVII ##STR18## wherein R₁ is C₁ -C₄alkyl; R₂ is C₁ -C₄ alkyl or C₃ -C₆ cycloalkyl; and when R₁ and R₂ aretaken together with the carbon to which they are attached they mayrepresent C₃ -C₆ cycloalkyl optionally substituted with methyl; A isCOOR₈, CHO, CO₂ OH, COCO₂ OH, CONHCH₂ CO₂ OH, CONHOH, or ##STR19## R₈ ishydrogen, C₁ -C₁₂ alkyl optionally substituted with one of the followinggroups: C₁ -C₃ alkoxy, halogen, hydroxy, C₃ -C₆ cycloalkyl, benzyloxy,furyl, phenyl, furfuryl, halophenyl, loweralkylphenyl,loweralkoxyphenyl, nitrophenyl, carboxyl, loweralkoxycarbonyl, cyano, C₁-C₄ alkylthio or triloweralkylammonium, in addition the alkyl chain maybe interrupted by one or more O or S; C₃ -C₆ alkenyl optionallysubstituted with one of the following groups: C₁ -C₃ alkoxy, phenyl,halogen or with two C₁ -C₃ alkoxy groups or two halogen groups: C₃ -C₆cycloalkyl optionally substituted with one or two C₁ -C₃ alkyl groups;C₃ -C₁₀ alkynyl optionally substituted with phenyl, halogen or CH₂ OH:or a cation selected from the group consisting of alkali metals,alkaline earth metals, (Ca, Ba) and manganese, copper, iron, ammoniumand organic ammonium; R_(C) and R_(D) are H, or CH₃ ; B is H, COR₉ orSO₂ R₁₀, provided that when B is COR₉ or SO₂ R₁₀, and A is COOR₈, R₈cannot be hydrogen or a salt-forming cation; R₉ is C₁ -C₁₁ alkyl,chloromethyl or phenyl optionally substituted with one chloro, onenitro, one methyl, or one methoxy group; R₁₀ is C₁ -C₅ alkyl or phenyloptionally substituted with one methyl group, chloro or nitro; W is O orS; X is O, S, or --S=O; Y and Y' Z and Z' are hydrogen, halogen, C₁ -C₆alkyl, C₁ -C₄ hydroxyloweralkyl, C₁ -C₆ alkoxy, C₁ -C₆ acyloxy,benzoyloxy optionally substituted with one or two C₁ -C₄ alkyl, C₁ -C₄alkoxy, halogen; C₁ -C₄ alkylthio, phenoxy, C₁ -C₄ haloalkyl, C₁ -C₄haloalkoxy, nitro, cyano, C₁ -C₄ alkylamino., C₁ -C₄ dialkylamino, C₁-C₄ alkylsulfonyl or phenyl optionally substituted with-one or two C₁-C₄ alkyl, C₁ -C₄ alkoxy, halogen, or any combination of two of thesegroups and wherein Y and Z are the same group provided that Y and Z areH, halogen, alkyl or alkoxy, and when Y and Y' or Z and Z' are the samegroup they are hydrogen or alkyl; and the pyridine N-oxides thereof,when W is O or S and A is COOR₈ ; and when R₁ and R₂ are not the same,the optical isomers thereof, and, except when R₈ is a salt-formingcation, the acid addition salts thereof.

Oxidation of compounds of formula XXXVII when X is S yields novelthieno[3,4-b]pyridine 2,3-dicarboxylates which in a like manner to thatdescribed above and illustrated in Flow Diagram V above yields novelherbicidal 2-(2-imidazolin-2-yl)thieno[3,4-b]pyridine compounds offormula XXXVIIIb ##STR20## wherein R₁, R₂, A, B, W, Y and Z are asdescribed for formula XXXVI above.

The novel method of the present invention provides a means of preparinga wide variety of 5-substituted, 6-substituted and 5,6-disubstitutedpyridine-2,3-dicarboxylates including the novel formula XXXIbthieno[3,4-b]and furo[3,4-b]pyridine 2,3-dicarboxylates described above.

Literature methods for preparing 5,6-dialkyl and5,6-alkyl-arylpyridine-2,3-dicarboxylates are limited, often requiringoxidation of alkyl or aryl substituents at positions 2 and 3 in order toobtain diacids. R. Jones, J. Am. Chem. Soc. 73, 4380 (1951) describes amethod in which reaction of a primary enamine yields6-alkylpyridine-2,3-dicarboxylates which contain electron withdrawingsubstituents such as COCH₃, CN or CO₂ Et in the 5-position. This methodcannot be used to prepare 5,6-dialkyl or alkylarylpyridine-2,3-dicarboxylates because primary enamines without electronwithdrawing substituents cannot readily be prepared, i.e., the reactionof ammonia with aliphatic ketones produces imines which do nottautomerize to enamines and, unless trapped in situ, polymerize. Othermethods employing malononitriles such as those described in JapanesePatent 78 69,835 and that of 3. I. DeGraw, J. Het. Chem. 19, 1461(1982), can yield 5, and 5,6-dialkylpyridines but not with the desired2,3-dicarboxylate substitution directly.

The method of the present invention utilizing enamines of formula XXXIVwhich react with formula XXXV oxymethylene oxalacetates and subsequentaddition of an ammonia source produces pyridine 2,3-dicarboxylates withsubstituents in the 5, 6, or 5 and 6 positions directly and does notlimit these substituents to those which are electron withdrawing.

Thus, pyridine-2,3-dicarboxylates containing substituents in the 5and/or 6 position may conveniently be prepared by admixing essentiallyequimolar amounts of a formula XXXIV enamine and a formula XXXVoxalacetate in a suitable solvent and stirring the resulting reactionmixture for from five minutes to 24 hours at a temperature of from -78°C. to 50° C. Treatment of the thus-formed adduct with a minimum of 1molar equivalent of ammonia or an ammonia source and continued stirringfor from 0.5 to 72 hours at a temperature of from 0° C. to the boilingpoint of the mixture gives the desired pyridine-2,3-dicarboxylate whichmay be isolated by standard laboratory techniques such as extraction orcolumn chromatography.

Many fused heteropyridine diesters of the general formula XXXI may beobtained by oxidative cleavage of appropriately substitutedheteroquinoline compounds which may be prepared by the method of O.Meth-Cohn, J. Chem. Soc., Perkin I, 2509 (1981), directly, or cleavagefollowed by reactions with amines, hydrazines, hydroxide or hydrogensulfide or a sulfide salt as illustrated in Flow Diagram VII below:##STR21## wherein D-E together with the aromatic carbons to which theyare joined, represents a five- or six-membered fused heterocyclic ringcontaining one or two N or NR₃ ; oxygen or sulfur; m is an interior of 1or 2.n is an integer of from 1 to 3 but must be 3 in the case ofreaction with Na₂ S or NaSH; m plus n=3 or 4; R is hydrogen, CH₃ or C₂H₅ and R₃ is as described in Formula I-XXIV.

Another general approach to obtaining fused heteropyridine diesterswhich are useful as intermediates for the preparation of the novelformula I-XXIV compounds of the invention is ring closure of5-nitro-6-disubstituted pyridine-2,3-dicarboxylic acid esters, which maybe prepared by the reaction of an ethoxymethyleneoxalacetate ester withnitroacetone or nitroacetamide.

For example, pyrrolopyridines may be prepared by condensation of5-nitro-6-methylpyridine-2,3-dicarboxylates with N,N-dialkyl carboxylicamide diacetals, followed by reduction and concomitant cyclization,depending on reaction conditions. Alkylation of the product gives amixture of two NR₃ compounds, where R₃ is alkyl or alkoxy, asillustrated in Flow Diagram VIII below, wherein R₃ and R₄ are asdescribed for formulas I-XXIV above. ##STR22## wherein R₃ is C₁ -C₄alkyl.

5-Acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylic acid esters,[referred to as keto-pyridone diesters, which may readily be prepared byadding sodium acetate to a stirred mixture of dialkyl (ethoxymethylene)oxalacetate and acetoacetamide in an alcohol] provide a source of avariety of fused heteropyridine-2,3-dicarboxylate esters which areuseful as intermediates for the preparation of herbicidal(2-imidazolin-2-yl) fused heteropyridine compounds of the invention.

Pyranopyridine diesters may be prepared from the5-acetyl-6-pyridone-2,3-dicarboxylates, by condensation with N,N-dialkylcarboxylic acid dineopentyl acetals giving enaminone intermediates whichcyclize with acid to the pyranone compounds. Further reduction and/oralkylation and dehydration can give a variety of intermediates dependingon the selected conditions.

Additionally, an acetyl pyridone may be condensed with an appropriatelysubstituted carboxylic acid (phenylacetic acid for example), which maybe reduced to the pyranopyridine diesters. Other keto-pyridone diestersgive similar compounds with various alkyl substituents in place of4-methyl.

Condensation of ketopyridones with dialkyl oxalates give intermediateswhich are cyclized by acid catalysis.

5-Acetyl-6-pyridone-2,3-dicarboxylates also can undergo reaction withperacids to give the 5-hydroxy-6-pyridine-2,3-dicarboxylates, or formoximes which can undergo rearrangement and after hydrolysis, yield5-amino-6-pyridone-2,3-dicarboxylates.

These 5-amino and 5-hydroxy compounds may be utilized as intermediatesfor the preparation of oxazolo, morpholino, dioxolo and dioxanopyridinediesters. These reaction sequences are in general illustrated in FlowDiagrams IXa to IXe below. ##STR23##

6-Pyridone-2,3,5-tricarboxylic esters can be prepared by condensation ofan ester amide with an ethoxymethylene oxalacetate ester and thenconverted to the 6-chloro compound. The later chloro compound may thenbe employed in the synthesis of pyrrolopyride diesters by reaction of anN-substituted amino acid ester, with added base, followed by cyclizationusing alkoxide as illustrated in Flow Diagram X below. The resultingpyrrolopyridine compounds can be further alkylated, selectivelydecarboxylated, reduced and/or debydrated to a variety of substitutedcompounds. ##STR24##

Other diester compounds are prepared by a novel reaction which employs athermal Dieis-Alder Reaction of an appropriately substituted asymmetrictriazine diester, followed by loss or nitrogen. An example of this typeof reaction sequence is described by G. Seitz and S. Dietrich, Arch.Pharm., 317,379 (1984). Asymmetic triazine diesters which are useful inthis reaction are prepared from substituted open chain precursors,containing one or more heteroatoms in the chain, by reaction withdialkyl 2,3-dioxosuccinate. Open chain precursors may be prepared, forexample, from methylthiosemicarbazide and an 1-alkynyl alcohol, amine ormercaptan. Certain other triazine intermediates may be prepared from anamidrazone, prepared via the nitrile. The triazine need not be isolated;heating can continue until the desired product is formed.

These reactions are illustrated in Flow Diagrams XI and XII below.##STR25##

The formula I-IV and XVII-XX (2-imidazolin-2-yl)heteropyridines and theformula V-XVI imidazopyrrolopyridinediones of the present invention areexceedingly effective herbicidal agents useful for the control of anexceptionally wide variety of herbaceous and woody annual and perennialmonocotyledonous and dicotyledonous plants. Moreover, these compoundsare herbicidally effective for controlling weeds indigenous to both dryland and wet land areas. They are also useful as aquatic herbicides andare unique in their effectiveness in controlling the above-said plantswhen applied to the foliage thereof or to the soil or water containingseeds or other propagating organs of said plants such as tubers,rhizomes or stolons, at rates of from about 0.016 to 4.0 kg/ha, andpreferably at rates from about 0.032 to 2.0 kg/ha.

It is of course obvious that the rates of application above the 4.0kg/ha level can also be used to effectively kill undesirable plantspecies; however, rates of application of toxicant above the levelnecessary to kill the undesirable plants should be avoided sinceapplication of excessive amounts of toxicant is costly and serves nouseful function in the environment.

Among the plants which may be controlled with the compounds of thisinvention are: Elatine triandra, Sagittaria pygmaea, Scirpus hotarui,Cyperus serotinus, Eclipta alba, Cyperus difformis, Rotala indica,Lindernia pyridonoria, Echinochloa crus-galli, Digitaria sanguinalis,Setaria viridis, Cyperus rotundus, Convolvulus arvensis, Agropyronrepens, Datura stramonium, Alopercurus myosuroides, Ipomoea spp., Sidaspinosa, Ambrosia artemisiifolia, Eichornia crassipes, Xanthiumpensylvanicum, Sesbahia exaltata, Arena fatua, Abutilon theophrasti,Bromus tectorum, Sorghum halepense, Lolium spp., Panicurndichotomiflorum, Matricaria spp., Amaranthus retroflexus, Cirsiumarvense and Rumex iaponicus.

It has been found that the formula I-IV, and XVII-XX(2-imidazolin-2-yl)fused heteropyridines and the formula V-XVIimidazopyrroloheteropyridinediones are generally selective herbicides,particularly effective for controlling undesirable weeds in the presenceof leguminous crops such as soybeans, and cereal crops such as wheat,barley, oats and rye. However, certain compounds are less selective thanothers in this series.

It has also been found that several of the formula (2-imidazolin-2-yl)fused heteropyridines are effective as antilodging agents in cerealcrops when applied at rates of application between about 0.5 to 2000 gper hectare. At rates of application not exceeding about 2000 g perhectare, it has also been found that certain of these compounds areeffective for increasing branching of leguminous crops and tillering ofcereal crops. At rates of application not exceeding 2000 g per hectare,certain of these compounds are useful as dwarflug agents for turf.

Those imidazolinyl fused heteropyridines and derivatives, wherein R₈ isa salt-forming cation, which are water soluble, can simply be dispersedin water and applied as a dilute aqueous spray to the foliage of plantsor to soil containing propagating organs thereof. These salts also lendthemselves to formulation as flowable formulations.

Other fused heteropyridine compounds wherein R₈ is a salt-forming cationor represents an ester which is not water soluble lend themselves toformulation as emulsifiable concentrates, thus providing a wide range offormulation options for specific purposes.

The (2-imidazolin-2-yl) fused heteropyridines can also be formulated aswettable powders, flow concentrates, granular formulations and the like.

Wettable powders can be prepared by grinding together about 20% to 45%by weight of a finely divided carrier such as kaolin, bentonire,diatomaceous earth, attapulgite, or the like, 45% to to 80% by weight ofthe active compound, 2% to 5% by weight of a dispersing agent such assodium lignosulfonate, and 2% to 5% by weight of a nonionic surfactant,such as octylphenoxy polyethoxy ethanol, nonylphenoxy polyethoxy ethanolor the like.

A typical flowable liquid can be prepared by admixing about 40% byweight of the active ingredient with about 2% by weight of a gellingagent such as bentonire, 3% by weight of a dispersing agent such assodium 1 ignosulionate, 1% by weight of polyethylene glycol and 54% byweight of water.

A typical emulsifiable concentrate can be prepared by dissolving about5% to 25% by weight of the active ingredient in about 65% to 90% byweight of N-methylpyrrolidone, isophorone, butyl cellosolve,methylacetate or the like and dispersing therein about 5% to 10% byweight of a nonionic surfactant such as an alkylphenoxy polyethoxyalcohol. This concentrate is dispersed in water for application as aliquid spray.

When the compounds of the invention are to be used as herbicides wheresoil treatments are involved, the compounds may be prepared and appliedas granular products. Preparation of the granular product can beachieved by dissolving the active compound in a solvent such asmethylene chloride, N-methylpyrrolidone or the like and spraying thethus prepared solution on a granular carrier such as corncob grits,sand, attapulgite, kaolin or the like.

The granular product thus prepared generally comprises about 3% to 20%by weight of the active ingredient and about 97% to 80% by weight of thegranular carrier.

In order to facilitate a further understanding of the invention, thefollowing examples are presented primarily for the purpose ofillustrating certain more specific details thereof. The invention is notto be deemed limited thereby except as defined in the claims. Unlessotherwise noted, all parts are by weight.

EXAMPLE 1 Preparation of diethyl1,6-dihydro-5-nitro-6-oxo-2,3-pyridinedicarboxylate ##STR26##

Diethyl(ethoxymethylene)oxalacetate (5.63 g, 0.023 mol,) is dissolvedunder N₂ atmosphere in 20 mL of absolute ethanol and cooled to 0° C.Nitroacetamide (2.00 g, 0.019 mol,) (S. K. Brownstein, J. Org. Chem 23,113 (1958)) and sodium acetate (1.56 g, 0.019 mol,) are added and themixture is stirred at room temperature for 15 hours. The suspension isdiluted with 15 mL of absolute ethanol and acidified to pH 2 withconcentrated HCl. The inorganics are removed by filtration and thefiltrate is concentrated to an oily solid which is gravitychromatographed, first with methylene chloride and then 2% methanol inmethylene chloride. The fractions are combined and stripped to give 4.28g of the title product as a yellow solid, 78.4% yield, melting point144°-145° C.

EXAMPLE 2 Preparation of diethyl6-chloro-5-nitro-2,3-pyridinedicarboxylate ##STR27##

Diethyl 1,6-dihydro-5-nitro-6-oxo-2,3-pyridinedicarboxylate (26.23 g,0,092 mol) is partially dissolved under N₂ atmosphere in 250 mL ofphosphorous oxychloride and the mixture is heated to 80° C. for 15hours. The mixture is cooled and concentrated and the resulting oildissolved in ethyl acetate and washed with water, 10% K₂ CO₃ and brine.The organic layer is dried over MgSO₄, filtered and the solvent removedto yield a solid which is recrystallized from absolute ethanol/water togive 20.65 g of the produce as a brown solid in 73.9% yield, having amelting point of 84.5°-86° C.

EXAMPLE 3 Preparation of diethyl6-amino-5-nitro-2,3-pyridinedicarboxylate ##STR28##

Diethyl 6-chloro-5-nitro-2,3-pyridinedicarboxylate (20.59 g, 0.068 mol)is suspended in 500 mL of absolute ethanol and the solution cooled to 0°C. Gaseous ammonia is bubbled in for one hour, causing an exotherm to20° C. The mixture is concentrated to a brown solid and partitionedbetween ethyl acetate and water. The organic layer is dried over Na₂SO₄, filtered and the solvent removed to yield a yellow solid, meltingpoint 120°-122° C.

EXAMPLE 4 Preparation of diethyl 5,6-diamino-2,3-pyridinedicarboxylate##STR29##

Diethyl 6-amino-5-nitro-2,3-pyridinedicarboxylate (5.00 g, 0.0176 mol)is suspended in 250 mL of absolute ethanol and the mixture cooled to 0°C. Palladium on carbon (50 g of 10% is added and the mixture is shakenunder 50 psi hydrogen in a Parr apparatus for four hours. The catalystis removed by filtration through a pad of Celite, and the filtrate isconcentrated to yield 4.21 g (94.2%) of product as a yellow solid,melting point 143°-146.5° C.

EXAMPLE 5 Preparation of diethyl2-methyl-imidazo[4,5-]b]pyridine-5,6-dicarboxylate ##STR30##

Diethyl 5,6-diamino-2,3-pyridinedicarboxylate (10.38 g, 0.041 mol) isstirred under an N₂ atmosphere in 100 mL glacial acetic acid, to give aclear orange solution. Triethylorthoacetate (TEOA), (0.19 mol) is thenadded and the mixture is heated to reflux for 15 hours. The cooledsolution is poured into ice water and neutralized with ammoniumhydroxide. The solution is extracted with ethyl acetate, the combinedorganic layers washed with brine, dried over Na₂ SO₄, filtered andconcentrated to an oil. The oil is taken up in ethyl acetate and thedesired product is precipitated by the addition of hexanes in two cropsof beige solid, totalling 8.11 g (71.3%), having a melting point of164°-165° C.

EXAMPLE 6 Preparation of diethyl1,2-dimethyl-1H-imidazo[5,4-b]-pyridine-5,6-dicarboxylate (Isomer A) anddiethyl 1,2-dimethyl 1H-imidazo[4,5-b]pyridine-5,6-dicarboxylate (IsomerB) ##STR31##

Diethyl 2-methylimidazo[4,5-b]pyridine-5,6-dicarboxylate (8.11 g,0.029mol,) is suspended in 250 mL THF. Sodium hydride (1.61 g, 607,dispersion in mineral oil, 0.040 mol) is added in one portion, causingan exotherm to 34° C. Methyl iodide (3.6 mL, 0.058 mol) is added,causing the precipitation of a large amount of solid. THF, 150 mL isthen added and the suspension stirred at room temperature for 15 hours.The mixture is poured into 500 mL water and the mixture extracted withmethylene chloride. The organic layers are combined, washed with brine,dried over Na₂ SO₄ and concentrated to give 5.59 g of a brown solid.

The aqueous layer is concentrated to a solid which is triturated withethyl acetate and filtered. The filtrate is concentrated to yield 0.59 gof a black oil and the solid is suspended in acetone and heated toreflux. The suspension is filtered, and the filtrate is stripped to 1.82g of a yellow solid.

The solid obtained by extraction and the oil are mixtures of isomers.The yellow solid obtained from the boiling acetone is primarily isomerB.

The isomer mixture is separated by chromatography, first using methylenechloride, then 1% methanol in methylene chloride, yielding the purifiedfaster moving isomer A as an oil (0.9 g). Structural assignments of Aand B are made on the basis of ¹³ C NMR spectroscopy.

EXAMPLE 7 Preparation of 4-amino-1-methylpyrazole ##STR32##

1-Methyl-4-nitropyrazole (6.00 g, 0.047 mol) (M. E. Foster and J. Hurst,J. Chem. Soc. Perkin 1,507,(1976)) is dissolved in 185 mL of methanoland cooled while 0.47 g of 10% palladium on carbon is added. The mixtureis shaken for 15 hours under 50 psi hydrogen in a Parr hydrogenator. Thecatalyst is removed by filtration through a pad of celite and thefiltrate concentrated to give a red oil which is used immediatelywithout characterization or purification.

EXAMPLE 8 Preparation of dimethyl[1-methylpyrazol-4-yl)amino]butenedicarboxylate ##STR33##

Dimethylacetylenedicarboxylate (6.4 mL, 0.052 mol) is dissolved in 75 mLmethylene chloride and the mixture cooled to 0° C. Unpurified4-amino-l-methylpyrazole (assumed to be 4.58 g, 0.047 mol) is dissolvedin 25 mL methylene chloride and added dropwise so that the reactiontemperature remains below 5° C. The solution is stirred for one hour,and is then allowed to warm to room temperature and stirred for 65hours. The mixture is concentrated and the resulting oil is used withoutcharacterization or purification.

EXAMPLE 9 Preparation of dimethyl1-methylpyrazolo[4,3-b]pyridine-5,6-dicarboxylate ##STR34##

Dimethylformamide (7.4 mL, 0.096 mol) is dissolved in 125 mLdichloroethane and the mixture cooled to -5° C. in an acetone/ice bath.Phosphorous oxychloride (8.9 mL, 0.095 mol) is added in one portion andthe clear colorless solution is allowed to warm slowly to roomtemperature, gradually turning yellow. The unpurified dimethyl[(1-methylpyrazol-4-yl)amino]-butenedicarboxylate is dissolved in 75 mLof dichloroethane and added to the chilled Vilsmeier reagent dropwisekeeping the reaction temperature below 5° C. The mixture is allowed towarm slowly to room temperature over four hours, and then is heated toreflux for one hour. The mixture is concentrated to a solid which ischromatographed using 3:1 hexanes/ethyl acetate. The fractionscontaining the desired product are combined and concentrated to give theproduct as a white solid (16.93 g, 71.4%), melting point 148°-149° C.

EXAMPLE 10 Preparation of 3-methyl-5-amino isoxazole ##STR35##

Hydroxylamine hydrochloride (34.81 g, 0.50 mol) is dissolved in 100 mLwater and the solution cooled in an ice bath for ten minutes. Then3-aminocrotononitrile (48.30 g of 85%, 0.50 mol) is added portionwiseover ten minutes. After stirring for 30 minutes, the solution turnsorange and a solid precipitates. The solid is collected by filtrationand recrystallized from benzene, giving the product (30.98 g, 63.2%) asa white solid, having a melting point of 77°-79° C.

EXAMPLE 11 Preparation of diethyl3-methylisoxazolo[5,4-b]pyridine-5,6-dicarboxylate ##STR36##

5-Amino-3-methylisoxazole (12.25 g, 0.125 mol) anddiethyl(ethoxymethylene)oxalacetate (33.55 g, 0.138 mol) are dissolvedin 200 mL glacial acetic acid under an N₂ atmosphere. The solution isheated to reflux for two hours, then stirred at room temperature for 65hours. The solution is poured into ice water, causing the precipitationof a red solid. The solid is collected by filtration, redissolved in 175mL glacial acetic acid and reprecipitated with the addition of ice. Theresulting yellow solid is collected by filtration and air dried, giving14.20 g of product, yield 40.8%, having melting point 95°-99° C. A smallamount is recrystallized from hexanes/ethyl acetate, melting point100°-101° C.

EXAMPLE 12 Preparation of diethyl6,7-dihydro-5H-pyridine-2,3-dicarboxylate ##STR37##

To a solution of diethyl ethoxymethyleneoxalacetate (10.25 g, 0.042mol)dissolved in ethanol (100 mL) at 0° is added1-morpholinocyclopentene (6.8 mL, 0.042 mol). After an initial exothermto 9°, the reaction is stirred at 5° for 20 minutes. Concentrated NH₄ OH(20 mL) is added and the reaction solution is heated to reflux for 30minutes, concentrated in vacuo to an oil, diluted with H₂ O (100 mL),and extracted with CH₂ Cl₂. Chromatography of the extract over silicagel with hexane-ethyl acetate (7:3) elution gives the product as an oil(5.06 g. 0.019 mol, 46%).

EXAMPLE 13 Preparation of diethyl 5-ethylpyridine-2,3-dicarboxylate##STR38##

Diethyl ethoxymethyleneoxalacetate (3.17 g, 0.013 mol) is added to asolution of 1-morpholinobutene (1.84 g, 0,013 mol) dissolved in CH₂ C₁₂(40 mL) at 0°. The solution is concentrated in vacuo, and ammoniumacetate (50 g), ammonium hydroxide (10 mL), tetrahydrofuran (20 mL) and95% ethanol (20 mL) are added. The solution is heated to reflux for 30minutes, then held at 3° for 72 hours. The reaction solution is thenpartitioned between water and ethyl acetate. The organic layer is driedover sodium sulfate and concentrated in vacuo to give the product (1.85g, 0.0074 mol, 57%).

EXAMPLE 14 Preparation of diethyl 5-ethylpyridine-2,3-dicarboxylate##STR39##

To a solution of diethyl ethoxymethyleneoxalacetate (43.2 g, 0.16 mol)dissolved in CH₃ OH (150 mL) at -10° under N₂ is added1-morpholinobutene (25 g, 0.16 mol). The reaction is slowly warmed toroom temperature over three hours, after which the CH₃ OH is removed invacuo. The residue is dissolved in acetic acid (100 mL) and thissolution slowly added to NH₄ Cl (34.2 g, 0.64 mol) dissolved in aceticacid (200 mL) at 50°-70°. The reaction is then heated to 90°-95° for twohours and 30 minutes, concentrated in vacuo, partitioned between waterand the CH₂ Cl₂, and the organic phase chromatographed over silica gelwith CH₂ Cl₂ -CH₃ CN (95:5) elution to give the product as an oil.Distillation at 123°-155° at 0.15mm gives the product (23.4 g, 83% pure,55%).

EXAMPLE 15 Preparation of diethyl6,7-dihydro-5H-pyridine-2,3-carboxylate ##STR40##

Diethyl hydroxymethyleneoxalacetate is prepared by the method of R.Jones, J. Am. Chem. Soc. 73, 3684 (1951).

Diethyl hydroxymethyleneoxalacetate (5.0 g, 0.0231 mol) is dissolved inethanol (50 mL) under N₂ and cooled to 3°. To this is added1-morpholinocyclopentene (3.7 mL, 0.231 mol). The reaction is stirredfor 20 minutes at a temperature of 3°-7° C., then treated withconcentrated NH₄ OH (10 mL), stirred at room temperature overnight, thenconcentrated in vacuo. The residue is partitioned between CH₂ Cl₂ and H₂O, and after further extraction of the aqueous layer with CH₂ Cl₂, thecombined organic layers are dried over Na₂ SO₄ and concentrated in vacuoto an orange oil. Chromatography over silica gel withhexane-ethylacetate (4:1) elution gives the product as a yellow oil(0.85 g, 0.0032 mol, 14%).

EXAMPLE 16 Preparation of diethyl5,7-dihydro[3,4-h]pyridine-2,3-dicarboxylate and diethyl2,3-dihydrofuro[2,3-b]pyridine-5,6-dicarboxylate ##STR41##

To a solution of tetrahydrofuran-3-one (J. Pharm. Sci., 59, 1678 (1970);46.5 g, 0.540mol) in benzene (250 mL), stirred at room temperature, isadded piperidine (45.98 g, 0.540 mol) and p-toluenesulfonic acidmonohydrate (0.46 g, 0.002mol). The mixture is heated at reflux under aDean-Stark trap for four hours, cooled and stripped to a dark brown oilconsisting of a 1:1 mixture of 2,3- and 2,5-dihydrofuran enamines (I andII; Recl. Trav. Chim., 92,865 (1973)). Then ethanol (500 mL) and diethylethoxymethylene oxalacetate (178.79 g, 1.35 mol) is added and stirringcontinued for 45 minutes. Ammonium acetate (1.24.87 g, 1.62 mol) isadded and the mixture is beated at reflux for 45 minutes. After cooling,the solvents are removed and the off-white solids diethyldihydrofuro[3,4-b]pyridine-5,6-carboxylate and diethyldihydrofuro[3,2-b]pyridine-5,6-carboxylate are separated bychromatography, on silica gel, eluting with hexaneethyl acetate. Themass spectrum shows the parent peak (M+H/e) for both compounds at 266.

EXAMPLE 17 Preparation of 5,7-dihydro[3,4-b]pyridine-2,3-dicarboxylicacid ##STR42##

The diester (6.64 g, 0,025 mol) is added to ethanol (50 mL) and water(50 mL), the mixture treated with NaOH (10.0 g, 0.25 mol) and stirred atroom temperature for three days. The mixture is then heated to refluxfor one hour, diluted with water (50 mL) to dissolve remaining solids,and again heated to reflux for three hours. The ethanol is removed fromthe reaction in vacuo, leaving an aqueous solution that is acidifiedwith concentrated HCl, then concentrated in vacuo to a solid. The solidis extracted with first acetone, and then hot ethanol. The combinedextracts are concentrated in vacuo to give the diacid (2.93 g, 0.014mol, 56% yield).

EXAMPLE 18 Preparation of 5,7-dihydro[3,4-b ]pyridine-2,3-dicarboxylicacid anhydride ##STR43##

The diacid 5,7-dihydrofuro[3,4-b]pyridine-2,3-dicarboxylic acid (2.93 g,0,014 mol) is added to the acetic anhydride (100 mL) and the mixtureheated to 90° for three hours. Solids (0.25 g) are removed by filtrationand the filtrate concentrated in vacuo. The initial precipitate iscombined with the concentrate to give 5 7-dihydro[3 4-b]pyridine-23-dicarboxylic acid anhydride.

EXAMPLE 19 Preparation of5,7-dihydro-3-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)furo[3,4-b]pyridine-2-carboxylicacid ##STR44##

The anhydride (2.52 g, 0.013 mol) is dissolved in THF (100 mL) andtreated with the amino amide (1.95 g, 0.015 mol). This mixture isstirred at room temperature overnight, then another portion of aminoamide (1.95 g, 0.015 mol) is added. The reaction is refluxed for 2.5hours, cooled and concentrated in vacuo. The residue is dissolved in H₂O (80 mL) and NaOH (3.12 g, 0.078 mol). This solution is heated at 8.5°for one hour, then stirred at room temperature overnight. The reactionis then heated again at 85° for two hours, cooled, acidified with conc.HCl to pH 2-3, and filtered. The desired product is found in thefiltrate which is concentrated in vacuo, then disolved in methanol andpassed thru a small pad of silica gel to remove the polar material. Themethanol fractions are column chromatography over silica gel withHexane: EtOAc (19:1) elution to give the product as a pale yellow solid(0.55 g, mol, 14% yield); mp 115°-118° . Mass spectrum M+H=304.

EXAMPLE 20 Preparation of diethyldihydrothieno[3,2-b]pyridine-5,6-dicarboxylate ##STR45##

To a solution of tetrahydrothiopene-3-one (Maybridge Chem. Co.; 20.0 g,0.196 mol) in benzene (100 mL), stirred at room temperature, is addedpiperidine (16.7 g, 0.196 mol) and p-toluenesulfonic acid monohydrate(0.20 g, 0.001 mol). The mixture is heated at reflux under a Dean-Starktrap for four hours, cooled and stripped to a dark brown oil consistingof a 1:1 mixture of 2,3- and 2,5-dihydrothiophene enamines (Recl. Trav.Chim., 92, 865 (1973)).

To the above enamine mixture is added ethanol (100 mL) and diethylethoxymethylene oxalacetate (72.1 g, 0.294 mol) and stirred for 45minutes. Ammonium acetate (45.3 g, 0.588 mol) is added in one portionand the mixture is heated at reflux for 45 minutes.

After cooling, the solvents are stripped and the yellow solid diethyldihydrothieno[3,2-b]pyridine-5,6-dicarboxylate product is obtained bychromatography after eluting with nexane-ethyl acetate. The massspectrum shows the parent peak (M+H/e) at 282.

Utilizing the above procedure and substituting the appropriate enamineyields the compounds listed in Table I below.

    TABLE I          Ammonium      Enamine Solvent A Time A Temp A Source Solvent B Time     B Temp B Yield Product      ##STR46##      THF 2 hrs  0-25° EtOH+NH.sub.4      OAc     ##STR47##      ##STR48##      EtOH 90 min 3-7° NH.sub.4      OH EtOH 45 min Reflux 60%     ##STR49##      ##STR50##      EtOH 150 min  0- 50° NH.sub.4 OH+NH.sub.4 OAc EtOH 24 hrsat     25°then1 hrat 60° 25-60°      ##STR51##      ##STR52##      CH.sub.2 Cl  0° NH.sub.4 OH+NH.sub.4 OAc THF+EtOH(1:1) 30     minatrefluxthen48 hrsat 5° 5°-reflux 43%      ##STR53##      ##STR54##      CH.sub.3 OH 3 hrs 10-25° Nl.sub.4 Cl HOAc 2.5 hrs 90-95°     54%      ##STR55##      ##STR56##      THF 2 hrs  0-25° NH.sub.4 OH+NH.sub.4      OAc EtOH     ##STR57##      ##STR58##      CH.sub.2 Cl.sub.2 2 hrs  3-25° NH.sub.4 OH+NH.sub.4 OAc CH.sub.2     Cl.sub.2H.sub.2      O 65 hrs 25° 40%     ##STR59##      ##STR60##      EtOH 45 min 25° NH.sub.4      OAc EtOH 45 min reflux 34%     ##STR61##      ##STR62##      EtOH 45 min 25° NH.sub.4      OAc EtOH 45 min Reflux 8%     ##STR63##      ##STR64##             10%      ##STR65##

EXAMPLE 21 Preparation of triethyl5-(3-carboxy-3-hydroxyacryloyl)-1,6-dihydro-6-oxo-2,3-pyridenedicarboxylate##STR66##

To absolute ethanol 900 mL is added Na pellets (20.61 g, 0.896 mol, 5eq), giving a clear colorless solution. Diethyl5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate (50.00 g, 0.178mol,) is added in one portion, giving a finely divided pale yellowsuspension which is stirred at room temperature for one and one-halfhours. Diethyl oxalate (170 mL, 1.25 mol) diluted to 500 mL withabsolute ethanol is added over 45 minutes, giving a bright yellowsuspension, which is stirred at room temperature for one and one-halfhours. The mixture is poured into 1500 mL water and acidified to pH 2with concentrated HCl, giving the product as a yellow solid which iscollected by filtration, having a melting point 162°-16° C.

EXAMPLE 22 Preparation of triethyl4-oxo-pyrano[2,3-b]pyridine-2,6,7-tricarboxylate ##STR67##

The crude triethyl5-(3-carboxy-3-hydroxyacryloyl)-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate(82.16 g, 0.178 mol) is suspended under N₂ in 1000 mL xylene withstirring. 2-Toluenesulfonic acid (1.00 g) is added and the suspension isheated to reflux for twelve hours. The solution is filtered to removethe impurities from the starting material and the filtrate isconcentrated to a solid, which is recrystallized from methylenechloride/hexanes, giving the product as a yellow solid, (41.85 g. 64.8%over two steps having a melting point 106°-106.5° C.

EXAMPLE 23 Preparation of diethyl 1,8-naphthyridine-2,3-dicarboxylate##STR68##

2-Amino-3-formylpyridine (T. G. Majewicz and P. Caluwe, J. Org. Chem.39, 720 (1974); 37.1 g, 0.30 mol) is suspended under N₂ in 400 mlsabsolute ethanol with stirring. Then piperidine (3 mL) anddiethyloxalacetate (115 g, 0.61 mol, 2 eq) are added and the mixture isheated to reflux for 20 hours. Another 17 g diethyloxalacetate (0.09mol) is added and heating is continued for two hours. The mixture iscooled and concentrated to an oil which is chromatographed using 4:1hexanes/ethyl acetate, to give the product as a white to pale yellowsolid (52.00 g, 62.4%) melting point 88.5°-89.5° C.

Likewise, 1-methyl-4-amino-1,2,3-triazole-5-carboxaldehyde (ref: Chem.Pharm. Bull 27, 2861 (1979) is prepared in situ and condensed under theabove conditions to give diethyl1-methyl-1,2,3-triazole[5,4-b]pyridinedicarboxylate.

EXAMPLE 25 Preparation of diethyl3-(p-chloropbenyl)-4-methyl-2-oxo-2H-pyrano[2,3-b]pyridine-6,7-dicarboxylate##STR69##

Diethyl 5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate, (6.0 g,0.0213 mol), 4-chlorophenyl acetic acid (3.64 g, 0.0213 mol) andtriethylamine (3.0 g,.1.5 eq) are refluxed in 50 mL of acetic anhydridefor three and one-half hours and then stirred at room temperatureovernight. The reaction mixture is poured into 100 mL of ice cold waterand the pH is adjusted to 8 with an ammonium hydroxide solution. Thecrystalline solid is filtered, washed with water, dried and dissolved in100 mL of methylene chloride. The solution is dried over anhydroussodium sulfate and the solvent removed under reduced pressure to givethe desired product (8.8 g, 99%), which is crystallized from ethylacetate to give the pure product having a melting point 179°-181° C.

EXAMPLE 26 Preparation of diethyl3-(m-chlorophenyl)-4-methyl-2-oxo-2H-pyrano[2,3-b]pyridine-6,7-dicarboxylate##STR70##

Diethyl 5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate (12.0 g,0.043 mol), 3-chlorophenyl acetic acid (7.33 g, 0,043 mol) andtriethylamine (6.52 g) are refluxed in 120 mL of acetic anhydride forthree hours. The reaction mixture is cooled, poured into 120 mL ofice-cold water and made alkaline to pH 8 with an ammonium hydroxidesolution. The crystalline solid is filtered and washed with water togive (17.0 g, 95%) of the product after drying. Recrystallization fromethyl acetate affords the pure product (13.29, 74% yield), melting point170°-172° C.

EXAMPLE 27 Preparation of diethyl5-[3-(dimethylamino)acryloyl]-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate##STR71##

Diethyl 5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate, (25 g,0,089 mol) and N,N-dimethylformamide dineopentyl acetal (50 mL, 98%,40.62 g, 0.176 mol) are heated for 30 minutes at 80°-100° C. Aftercooling to room temperature, the product is obtained as a precipitateand is filtered and washed with hexane to yield 23.4 g, 70% yield, ofsolid which is recrystallized from isopropanol to give a pure product,melting point 182°-183° C.

EXAMPLE 28 Preparation of diethyl4-oxo-4H-pyrano[2,3b-]pyridine6,7-dicarboxylate ##STR72##

Diethyl5-[3-(dimethylamino)acryloyl]-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate(6 g, 0.0178 mol). and p-toluenesulfonic acid (4.5 g, 0.021 mol) inacetic acid (60 mL) are heated at reflux for three hours. The mixture isthen evaporated to dryness, neutralized with a saturated NaHCO₃ solutionand extracted with methylene chloride. The organic solution is driedover Na₂ SO₄, and concentrated to a thick oil, which solidifies aftertrituration with hexane-ether (4 g, 77%). The product is recrystallizedfrom isopropanol to give a melting point 71°-72° C.

EXAMPLE 29 Preparation of diethyl3,4-dihydro-4-hydroxy-2H-pyrano-2,3-b]pyridine-6,7-dicarboxylate and3,4-dihydro-4-oxo-2H-pyrano[2,3-b]pyridine-6,7-dicarboxylate ##STR73##

Diethyl 4-oxo-4H-pyrano[2,3-b]pyridine-6,7-dicarboxylate (8 g, 0.027mol)and palladium on carbon (0.8 g, 10%) suspended in ethanol (250 mL)and acetic acid (25 mL) are shaken under 50 psi hydrogen in a Parrapparatus for 16 hours. The mixture is filtered and the filtrateevaporated to dryness. The residue is neutralized with a saturatedNaHCO₃ solution and then extracted with methylene chloride and themethylene chloride solution dried over Na₂ SO₄. Evaporation of thesolvent gives the product mixture as an oil (8.34 g) which is purifiedby column chromatography to give the alcohol (4.4 g, 54%) and the ketone(2.4 g, 28%).

EXAMPLE 30 Preparation of diethyl2H-pyrano[2,3-b]pyridine-6,7-dicarboxylate and diethyl3,4-dihydro-2H-pyrano[2,3-b]-pyridine-6,7-dicarboxylate ##STR74##

Diethyl3,4-dihydro-4-hydroxy-2M-pyrano[2,3-b]-pyridine-6,7-dicarboxylate (4.4g, 0.015 mol), and p-toluenesulfonic acid (3.5 g, 0.018 mol) in toluene100 mL) are heated at 150° C. for one and one-half hours. The waterformed is azeotropically distilled and collected in a Dean-Stark trap.After cooling to room temperature, the reaction mixture is evaporated todryness and then neutralized with a saturated solution of NaHCO₃ andextracted with methylene chloride. The methylene chloride layer is driedover Na₂ SO₄ and evaporated to give (2.71 g) oil (65%). The massspectrum of this oil confirms the structure as2H-pyrano[2,3-b]pyridine-6,7-dicarboxylic acid, diethyl ester.

The oil (2.71 g, 0.0098 mol) and Pd/C (10%, 0.27 g) suspended in ethanol(60 mL) and reacted with 50 psi hydrogen in a Parr apparatus for one andone-half hours. The mixture is filtered and the filtrate evaporated togive (2.34 g) of the desired product as a white solid, which has amelting point 66°-67° C.

EXAMPLE 31 Preparation of dimethyl5-(2-chloroethyl)-6-chloro-2,3-pyridinedicarboxylate ##STR75##

Ozone gas is bubbled into a solution containing2-chloro-3-(2-chloroethyl)-5,8-dimethoxyquinidine (22.0 g); (O.Meth-Cohn, J. Chem. Soc., Perkin I, 1537-1543). trimethylorthoformate(80 mL) and H₂ SO₄ (2 mL) in methanol (1.0 L) over five hours and 45minutes. The mixture is concentrated under vacuum and the remaining oildissolved in ether and washed with saturated sodium bicarbonatesolution. The aqueous layer is extracted with additional ether. Thecombined ether extracts are washed with a 5% sodium bisulfite solutionand then saturated sodium chloride solution. The organic layer is driedover anhydrous magnesium sulfate and concentrated under vacuum affording16.5 g (71%) of dimethyl5-(2-chloroethyl)-6-chloro-2,3-pyridinedicarboxylate as an orange oil.

EXAMPLE 32 Preparation of dimethyl1-methyl-2,3-dihydro-1H-pyrrolo-2,3-b]pyridine-5,6-dicarboxylate##STR76##

Dimethylamine (7.5 g, 166.6 mol) is bubbled into a solution of dimethyl5-(2-chloroethyl)-6-chloro-2,3-pyridinedicarboxylate (20.0 g, 66mmol) inmethanol (400 mL) over three hours. The resulting solution is stirredfor 64 hours at room temperature and then four and one-half hours atreflux. After cooling the mixture is concentrated under vacuum and thecrude product chromatographed on 250 g silica using 2:1 hexanes:ethylacetate and then 1:1 hexanes:ethyl acetate as eluant, affording 2.32 g(14%) of dimethyl1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5,6-dicarboxylate, whichis recrystallized from methylene chloride/hexanes, having a meltingpoint 132°-133° C.

EXAMPLE 33 Preparation of dimethyl1-methyl-1H-pyrrolo[2.3-b]pyridine-5,6-dicarboxylate ##STR77##

To a solution of 2.53 g (0,010 mol) dimethyl2,3-dihydro-1-methyl-1H-pyrrolo[2,3-b]pyridine-5,6-dicarboxylate in 40mL dioxane is added 2.64 g (0.011 mol)2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The resulting solution isstirred for 17 hours at 250° C. and for three hours at reflux. Thedioxane is removed under vacumn and the residue is partitioned between100 mL CH₂ Cl₂ and 100 mL at NaHCO₃ and filtered. The layers areseparated and the aqueous fraction is extracted with 2×75 mL CH₂ Cl₂.The combined CH₂ Cl₂ solutions are dried over MgSO₄ and are concentratedunder vacuum. The crude product is chromatographed on 50 g silica using2:1-hexanes:ethylacetate as eluant. Affords 1.90 g (75%) ofdimethoxy-1-methyl-1H-pyrrolo[2,3-b]-pyridine-5,6-dicarboxylate as ayellow solid, mp 132°-133° C.

EXAMPLE 34 Preparation oftriethyl-1,6-dihydro-6-oxo-2,3,5-pyridinetricarboxylate ##STR78##

A solution of ethylmalonamate (23.6 g, 0.18 mol) in absolute ethanol(300 mL) is added to a stirred solution of diethylethoxymethyleneoxalacetate (44.0 g, 0.18 mol) in ethanol (200 mL) at 0°C., followed by the addition, of solid sodium acetate (14.72 g, 0.18mol). After stirring for ten minutes at 0° C., the mixture is heated toreflux and stirred for 13.5 hours. After cooling, the ethanol is removedunder vacuum, and the residue diluted with water and acidified to pH 2with concentrated hydrochloric acid. The aqueous solution is extractedwith methylene chloride (2×200 mL) and the organic layer washed with 300mL saturated sodium chloride, then dried over anhydrous magnesiumsulfate and concentrated in vacuum to give 45.0 g of the title productas an orange oil.

EXAMPLE 35 Preparation of triethyl6-chloro-2,3,5-pyridine-tricarboxylate ##STR79##

A solution of triethyl 1,6-dihydro-6-oxo-2,3,5-pyridine-tricarboxylate(39.7 g) in 300 mL of phosphorous oxychloride and 0.5 mLdimethylformamide is stirred at 100° C. for four hours and 15 minutes.After cooling, the excess phosphorous oxychloride is removed undervacuum. The residue is taken up in 200 mL methylene chloride and thesolution poured into 500 mL of ice water and the layers are separated.The aqueous layer, made basic with concentrated ammonium hydroxide andice, is extracted with 150 mL methylene chloride. The combined methylenechloride extracts are dried over magnesium sulfate, filtered andconcentrated under vacuum, and the resulting crude product ischromatographed on silica using 5:1 hexanes:ethyl acetate and then 4:1hexanes:ethyl acetate as eluants affording 26.5 g (47%) of the titleproduct as an oil.

EXAMPLE 36 Preparation of tetraethyl6-[(carboxymethyl)methylamino]2,3,5-pyridinerticarboxylate ##STR80##

Sarcosine ethyl ester hydrochloride (13.91 g. 0.090 mol) is added to astirred solution of triethyl 6-chloro-2,3,5-pyridinetricarboxylate (26.2g, 0.075 mol) in tecrahydrofuran (THF, 200 mL) containing triethylamine(23 mL, 0.166 mol) at 0° C. The resulting solution is stirred for 24hours at room temperature. The triethylamine hydrochloride is removed byfiltration and is washed with 100 mL ether. The filtrate is concentratedunder vacuum and the crude product chromatographed on silica using 4:1hexanes:ethyl acetate as eluant affording 21.1 g (60%) of tetraethyl6-[(carboxymethyl)methylamino]-2,3,5-pyridinetricarboxylate as a yellowoil.

EXAMPLE 37 Preparation oftriethyl-3-hydroxy-1-methyl-1H-pyrrolo[2,3-b]pyridine-2,5,6-tricarboxylate##STR81##

Tetraethyl-6-[(carboxymethyl)methylamino]-2,3.5-pyridinetricarboxylate(0.3 g, 0.73 mmol) in ethanol (10 mL) is added to a freshly preparedsolution of sodium ethoxide (2.1 mmol) in ethanol at room temperature.The resulting orange solution is stirred for two hours at roomtemperature, then is poured into 200 mL water and the pH adjusted to 8with saturated aqueous sodium bicarbonate. The aqueous solution isextracted with methylene chloride (3×100 mL). The combined methylenechloride extracts are dried over anhydrous magnesium sulfate, filteredand concentrated under reduced pressure, affordingtriethyl-3-hydroxy-1-methyl-1H-pyrrolo[2,3-b]pyridine-2,5,6-tricarboxylate(0.28 g, 100%), which upon recrystallization from methylenechloride/hexanes has a melting point 129°-130° C.

EXAMPLE 38 Preparation of diethyl3-methyl-1H-pyrrolo[2,3-b]pyridine-5,6-dicarboxylate ##STR82##

A solution of triethyl3-hydroxy-1-methyl-1H-pyrrolo[2,3-b]pyridine-2,5,6-tricarboxylate (9.2g, 0.025 mol) in 75 mL 2N sodium hydroxide is heated at 60° C. for 21hours. After cooling to 0° C., the reaction mixture is acidified to pH 3with concentrated hydrochloric acid. The majority of the water isremoved by azeotropic distillation with toluene and the remainingsolution (25 mL) is diluted with 300 mL) methanol. To this solution isadded (3 mL) concentrated sulfuric acid and the resulting solution isheated for 64 hours at reflux. After cooling, the reaction mixture isconcentrated under vacuum and the residue partitioned between aqueoussodium bicarbonate (500 mL, 5%) and methylene chloride (300 mL). Thelayers are separated and the aqueous solution is extracted withadditional (200 mL) methylene chloride.

The combined organic extracts are washed with 200 mL saturated sodiumchloride solution, dried over anhydrous magnesium sulfate andconcentrated under vacuum. The crude product is chromatographed onsilica using 2:1 hexanes-ethyl acetate as an eluant, affording 2.04 g(29%) of diethyl3-methoxy-1-methyl-1H-pyrrolo[2,3-b]pyrrolo-[2,3-b]pyridine-5,6-dicarboxylate,mp 73°-74° C.

EXAMPLE 39 Preparation of diethyl5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate, 5-oxime ##STR83##

Hydroxylamine hydrochloride (4.94 g, 0.0711 mol) and sodium methoxide(7.68 g, 0.1422 mol) are added to a solution of diethyl5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate (20.00 g, 0.0711mol) dissolved in absolute ethanol (450 mL) under an N₂ atmosphere. Thereaction mixture is heated to reflux for 40 minutes and is then stirredat room temperature overnight. The mixture is then acidified to pH 4-5with glacial acetic acid and diluted with water (200 mL). The removal ofthe ethanol in vacuo results in the precipitation of an off-white solid,which is collected by filtration, washed with water, and air dried togive diethyl 5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate,5-oxime, melting point 140°-142° C.

EXAMPLE 40 Preparation of diethyl5-acetamido-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate and diethyl2-methyloxazolo-5,4-b]-pyridine-5,6-dicarboxylate ##STR84##

Thionyl chloride (35.5 mL, 0.486 mol) and three drops ofN,N-dimethylformamide are added to a solution of diethyl5-acetyl-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate, 5-oxime (47.99 g,0.162 mol) dissolved in chloroform (800 mL) under an N₂ atmosphere. Thereaction is stirred at room temperature for one hour, then stirred atroom temperature overnight.

The solution is concentrated in vacuo and the residue partitionedbetween methylene chloride and water. The two phase system isneutralized with 2M sodium hydroxide solution and the aqueous layerseparated and extracted with methylene chloride. The combined organicsolutions are dried over anhydrous sodium sulfate, concentrated in vacuoand chromatographed over silica gel with 1-30%/ethyl acetate inmethylene chloride to give diethyl5-acetamido-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate in 58% yield,which upon crystallization from methylene chloride/hexane has meltingpoint 149°-151° C.

The fractions enriched with the 2-methyloxazolopyridine arechromatographed over silica gel with hexane/ethyl acetate (3:1) eluant.Recrystallization of the product from methylene chloride/hexane givesdiethyl 2-methyloxazolo[5,4-b]pyridine-5,6-dicarboxylate as pale yellowcrystals in 17% yield having a melting point 101°-103° C.

EXAMPLE 41 Preparation of diethyl5-amino-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate ##STR85##

Hydrogen chloride gas is bubbled into a solution of diethyl5-acetamido-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate (5.2 g, 0.018mol) dissolved in absolute ethanol (400 mL) until the solution issaturated at 20° C. The reaction is stirred at room temperatureovernight and is then concentrated in vacuo. The resulting residue isdissolved in water, neutralized with solid sodium bicarbonate, andextracted into methylene chloride. The combined organic extracts aredried over anhydrous sodium sulfate, filtered and concentrated in vacuoto give diethyl 5-amino-1,6-dihydro-6-oxo-2,3-pyridinedicarboxylate as ayellow solid in quantitative yield.

EXAMPLE 42 Preparation of diethyl2-ethyloxazolo[5,4-b]pyridine-5,6-dicarboxylate ##STR86##

Diethyl 5-amino-1,6-dihydro-6-oxo-pyridine-2,3-dicarboxylate (7.57 g,0.030 mol), is suspended in 60 mL triethylorthopropionate (TEOP 0.30mol). A small amount of p-toluenesulfonic acid is added and the mixtureis heated at reflux for 65 hours. The triethylorthopropionate is removedin vacuo and the resulting oil is purified by column chromatography. Thetractions containing the pure desired product are combined and strippedto a honey-colored oil weighing 7.38 g, yield 84.8%.

EXAMPLE 43 Preparation of2-methyloxazole[5,4-b]pyridine-5.6-dicarboxylic acid ##STR87##

To a solution of diethyl 2-methyloxazolo[5.4-pyridine-5,6-dicarboxylate(5.42 g, 0.0195 mol) dissolved in absolute methanol (160 mL) is added a10% aqueous sodium hydroxide solution (36.1 mL, 0.0974 mol). A whiteprecipitate slowly forms. The reaction is stirred at room temperaturefor one hour, diluted with water (20 mL) to dissolve the precipitate,and concentrated in vacuo The residue is dissolved in water andacidified to pH 2-3 with concentrated HCl. The resulting whiteprecipitate is collected by filtration, washed with water, and air driedto give 2-methyloxazolo[5,4-b]pyridine-5,6-dicarboxylic acid in 61%yield, melting point 235°-236° C. (dec).

EXAMPLE 44 Preparation of2-methyloxazolo[5,4-b]pyridine-5,6-dicarboxylic anhydride ##STR88##

A suspension of 2-methyloxazolo[5,4-b]pyridine-5,6-dicarboxylic acid(4.84 g, 0.0218 mol) in acetic anhydride (150 mL) is slowly heated to70° C. at which point all the solids dissolve forming a yellow solution.The reaction mixture is heated at 70° C. overnight, cooled to roomtemperature, and concentrated in vacuo. Xylene is added to remove excessacetic anhydride by codistillation.2-Methyloxazolo[5,4-b]pyridine-5,6-dicarboxylic anhydride is obtained asa pale yellow solid in 97% yield melting point 194°-196° C.

EXAMPLE 45 Preparation of2-methyloxazolo[5,4-b]pyridine-5.6-dicarboxylic acid-6-diamide ##STR89##

The anhydride (4.33 g) is dissolved in 150 mL of acetonitrile and thesolution cooled in an ice bath and 3.03 g of the aminoamide is added. Awhite precipitate forms immediately. The reaction mixture is warmed toroom temperature and allowed to-stir overnight. The solid product isremoved by filtration, washed with acetonitrile, and dried in a vacuumoven, giving 6.3 g, 89%, mp 193°-196° C.

In a manner similar to the above other acid diamides and acid amidethioamides are prepared and appear in Table II below.

                  TABLE II                                                        ______________________________________                                        [1-Carbamoyl-1,2-dimethylpropyl)carbamoyl                                     heteropyridine carboxylic acids                                                ##STR90##                                                                    Heteropyridine            mp°C.                                        ______________________________________                                         ##STR91##                --                                                   ##STR92##                --                                                   ##STR93##                124-30                                               ##STR94##                --                                                   ##STR95##                --                                                   ##STR96##                --                                                   ##STR97##                --                                                   ##STR98##                --                                                   ##STR99##                193-196                                              ##STR100##               --                                                   ##STR101##               --                                                   ##STR102##               --                                                   ##STR103##               --                                                   ##STR104##               116                                                  ##STR105##               --                                                   ##STR106##               --                                                   ##STR107##               --                                                   ##STR108##               --                                                   ##STR109##               --                                                   ##STR110##               193-195                                              ##STR111##               188-190 (dec)                                        ##STR112##               --                                                   ##STR113##               --                                                   ##STR114##               --                                                   ##STR115##               --                                                   ##STR116##               138-141                                              ##STR117##               118-121                                              ##STR118##               72-75                                                ##STR119##               --                                                   ##STR120##               --                                                   ##STR121##               192-193                                              ##STR122##               --                                                   ##STR123##               --                                                   ##STR124##               --                                                   ##STR125##               --                                                   ##STR126##               --                                                   ##STR127##               --                                                   ##STR128##               --                                                   ##STR129##               --                                                   ##STR130##               --                                                   ##STR131##               --                                                   ##STR132##               --                                                   ##STR133##               --                                                  ______________________________________                                    

EXAMPLE 46 Preparation of diethyl1,6-dihydro-5-hydroxy-6-oxo-2,3-pyridinedicarboxylate ##STR134##

A solution of trifluoroperacetic acid is prepared by dropwise additionof trifluoroacetic acid (154 mL, 1.09 mol) into a 500 mL dioxanesolution containing 96 mL (0.94 mol) of 30% H₂ O₂ at 0° C. under N₂atmosphere.

2,3-Pyridinedicarboxylic acid, 5-acetyl-1,6-dihydro-6-oxo, diethyl ester(43.81 g, 0.156 mol) and K₂ HPO₄ (124.81 g, 0.716 mol) dissolved in 500mL dioxane in a three week reaction flask are added dropwise the abovetrifluoroperacetic and solution under N₂ atmosphere. The suspension isheated to 95° C. for 20 hours.

The mixture is filtered to isolate the inorganic salts. Evaporation ofthe filtrate gives an oil (35.84 g, 90%). NMR indicated about 90% pureof the desired product: MS, m/e =255.

EXAMPLE 47 Preparation of diethyl1,4-dioxino[2,3-b]pyridine-6,7-dicarboxylate ##STR135##

A mixture of 2,3-pyridinedicarboxylic acid,1,6-dihydro-5-hydroxy-6-oxo-, diethyl ester (17.55 g, 0.069 mol) andK2CO₃ (10.4 g, 0.075 mol) suspended in 100 mL of N,N'-dimethylacetamide(DMA) is heated to 100° C. under N₂ atmosphere. They 1,2-dibromoethane(14.2 g, 0.076 mol) in 20 mL DHA is added dropwise into the suspension.The resulting mixture is heated to 170° C. for 20 hours.

After cooling to room temperature, the mixture is filtered to remove theinsoluble salts. The filtrate is vacuum distilled over the residue isextracted with EtOAc. Evaporation of the EtOAc solution give 8.74 g ofdark oil. Mass spectrum of this oil indicates it contains about 50% ofthe desired product. The pure compound is obtained by liquid columnchromatography. MS, m/e=281. Yield of the desired product based on thestarting material, 21%.

EXAMPLE 48 Preparation of diethyl1,3-dioxolo[4,5-b]pyridine-5,6-dicarboxylate ##STR136##

A mixture of 2,3-pyridinedicarboxylic acid,1,6-dihydro-5-hydroxy-6-oxo-, diethyl ester (7.85 g, 0.031 mol) and K₂CO₃ (4.7 g, 0.034 mol) suspended in 80 mL DMA is heated to 100° C. underN₂ atmosphere. Then diiodomethane (8.5 g, 0.032 mol) in 20 mL DMA isadded dropwise into the suspension. The resulting mixture is heated to140° C. for 20 hours. The mixture is filtered to remove insoluble salts.The filtrate is vacuum distilled and the residue dissolved in CH₂ Cl₂.The CH₂ Cl₂ solution is passed through a thin column of silica-gel andcelite. Evaporation of CH₂ Cl₂ gives a light brown oil (1.83 g). Massspectrum of this oil suggests it contains about 33% of the desiredproduct. The pure compound is obtained by liquid column chromatography.MS, m/e, 267.

EXAMPLE 49 Preparation of diethyl7,8-dihydro-5H-pyrano[4,3-b]pyridine-2,3-dicarboxylate ##STR137##

A solution of diethyl ethoxymethyleneoxalacetate (2.33 g, 0.00954 mol)dissolved in absolute ethanol.(40 mL) is added dropwise to a cooled (5°C.) solution of 3,6-dihydro-N,N-dimethyl-2H-pyrano-4-amine (Hellberg, L.H., Juarez, A. Tet. Lett.., 3553 (1974)) (1.00 g, 0.00786 mol) dissolvedin ethanol (15 mL). The reaction is stirred at 5° C. for 30 minutes,treated with ammonium acetate (1.80 g 0.0233 mol), and stirred overnightat room temperature. The ethanol is removed in vacuo, and the residue ispartitioned between methylene chloride and water. The separated aqueouslayer is extracted with methylene chloride. The combined organicsolutions are dried over anhydrous sodium sulfate, concentrated invacuo, and chromatographed over silica gel with hexane/ethyl acetate(3:1) as eluant, to give diethyl7,8-dihydro-5H-pyrano[4,3-b]pyridine-2.3-dicarboxylate as a yellow oilin 72% yield.

EXAMPLE 50 Preparation of diethyl7,8-dihydro-5H-thiopyrano[4.3-b]-pyridine-2,3-dicarboxylate ##STR138##

Diethyl ethoxymethylene oxalacetate (6.50 g. 1.5 eq) is slowly added(ten minutes) to a solution of4-(3,6-dihydro-4H-thiopyran-3-yl)-morpholine (Verhoever et al.,Tetrahetron Lit; 209, 1977), (3.25 g, 1 eq) in 30 mL absolute ethanol at0° C. (ice bath). The mixture is magnetically stirred for one hour,whereupon ammonium acetate (3.75 g, 3 eq) is added and the mixture isheated at reflux and stirred for an additional three hours. The solutionis cooled and the solvent removed in vacuo. The viscons red syrup isflash chromatographed eluting with hexanes and gradually increasing theeluant polarity to 15% ethyl acetate/hexanes. The crystalline compoundis recrystallized (ether/heptanes) to afford 3.30 g (63%) of whitecrystals, mp 65°-66° C.

EXAMPLE 51 Preparation of ethyl2-formyl-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carboxylate ##STR139##

The diester (2.8 g) is dissolved in 100 mL toluene and chilled to -70°C. under a nitrogen atmosphere. Diisobutylaluminum hydride (DIBAL-H),(16 mL, 1 molar solution in toluene) is added dropwise over two hoursand then additional acetic acid, water and ether are added. A whitesolvent is removed by filtration and the filtrate concentrated in vacuoto yield an orange oil which is redissolved in methylene chloride,washed with brine, magnesium sulfate, filtered and the solvent removedto give the product as an oil.

Flash chromatography on silica gel using 1:1 hexanes ether give thealdehyde ester in 30% yield.

EXAMPLE 52 Preparation of ethyl 4-amino-1-methyl-2-pyrrolecarboxylate##STR140##

Ethyl 1-methyl-4-nitro-2-pyrrolecarboxylate (16.0 g, 0,081 mol) (M. J.Weiss, J. S. Webb and J. M. Smith, J. Amer. Chem. Soc., 79, 1266 (1957))is dissolved in (200 mL) ethanol and (1.60 g) of 10% platinum on carbonis then added. The mixture is shaken for 16 hours in a PARRhydrogenator. The catalyst is removed by filtration through a pad ofcelite and the filtrate is concentrated in vacuo to a yellow oil. Theoil is carried on directly without purification.

EXAMPLE 53 Preparation of 5-ethyl, dimethyl[(5-carboxy-1-methylpyrrol-3-yl)amino]maleate ##STR141##

Unpurified ethyl 4-amino-1-methyl-2-pyrrolecarboxylate (0.081 mol) isadded to (50 mL) anhydrous ether and (50 mL) water and the mixturecooled to 0° C. Dimethyl acetylenedicarboxylate (DMAD, 10.95 mL, 0.089mol) is dissolved in 25 mL anhydrous ether and added dropwise to thestirred mixture so that the reaction temperature remains below 15° C.After stirring cold for five minutes, sodium acetate is then added inportions until the pH of the aqueous layer is 9. The two-phase redmixture is then allowed to warm to room temperature and stirred for 15hours. The layers are separated, and the ethereal layer concentrated invacuo to give the product as a red oil which is carried on withoutpurification.

EXAMPLE 54 Preparation of 2-ethyl dimethyl1-methylpyrrolo[3.2-b]pyridine-2,5,6-carboxylate ##STR142##

Dimethylformamide (0.089 mol) is dissolved in 100 mL dichloroethane andcooled to 0° C. in an acetone/ice bath. Phosphorous oxychloride (0.089mol, 8.3 mL) is added dropwise over five minutes. The clear colorlesssolution is allowed to warm slowly to room temperature, whereupon itgradually turns yellow. Unpurified 5-ethyldimethyl-[(5-carboxy-1-methylpyrrol-3-yl)amine]maleate (0.081 mol) isdissolved in 50 mL dichloroethane and added dropwise to the cooledreagent so that the reaction temperature remains below 5° C. The mixtureis allowed to warm to room temperature and is then stirred for sixhours. The solution is quenched with ice and the resulting layersseparated. The organic layer is concentrated in vacuo to a brown solidwhich is recrystallized from ethyl acetate, yielding 21.3 g (82.1%) ofthe tan solid product, having a melting point 161.5°-163° C.

EXAMPLE 55 Preparation of diethyl6-methyl-5-nitro-2,3-pyridinedicarboxylate ##STR143##

Diethyl ethoxymethyleneoxalacetate (150.4 g, 0.616 mol, 1 eq) isdissolved in 300 mL absolute ethanol under a nitrogen atmosphere and themixture is cooled to -10° C. in an ice/acetone bath. Unpurified1-nitro-2-propanone (prepared by the method of D. Baker and S. Putt,Synthesis, 1978, 478-9, assumed to be 63.448 g, 0.616 mol) dissolved in100 mL absolute ethanol is then added to the stirred solution. Sodiumacetate (101.06 g, 1,232 mol) is then added in portions so that thetemperature of the reaction remains below 10° C., followed by theaddition of ammonium acetate (94.6 g, 1,232 g). The reaction mixture isallowed to warm to room temperature and is then stirred for 16 hours.The mixture is filtered through two pads of silica gel which are theneluted with methylene chloride. The filtrate is concentrated in vacuo toa thick dark oil which is chromatographed using hexanes as eluant,yielding the product in an 18.2% yield (31.4 g), having a melting point90°-91.5° C.

EXAMPLE 56 Preparation of diethyl6-[2-(dimethylamino)vinyl]-5-nitro-2,3-pyridinedicarboxylate ##STR144##

N,N-Dimethylformamide dimethylacetal (18.38 mL. 0.138 mol) is mixed withdiethyl 6-methyl-5-nitro-2.3-pyridinedicarboxylate (30.0 g, 0.106 mol).The solid mixture is heated to 55° C. for two hours and the resultingred soltuion is then cooled to room temperature. The solid, which formsupon cooling, is treated with anhydrous ether and the product collectedby filtration in 94% yield, having a melting point 128°-129.5° C.

Similarly, diethyl6-[2-(dimethylamino)propenyl]-5-nitro-2,3-pyridinedicarboxylate, havinga melting point 112°-113.5° C., is prepared in 93% yield fromN,N-dimethylacetamide dimethylacetal and diethyl6-methyl-5-nitro-2,3-pyridinedicarboxylate.

Diethyl 6-[2-(dimethylamino)styryl]-5-nitro-2,3-pyridinedicarboxylate isalso prepared, using the above method, from N,N-dimethylbenzamidediethyl acetal and diethyl 6-methyl-5-nitro-2,3-pyridinedicarboxylate. Amodification in the procedure of the latter is that upon cooling thedark red solution is partitioned between ether and water. The ethereallayer is separated and concentrated in vacuo to a dark red oil, whichwas carried on without purification.

EXAMPLE 57 Preparation of diethyl1-hydroxypyrrolo[3,2-b]pyridine-2,3-dicarboxylate ##STR145##

Diethyl 6-[2-(dimethylamino)vinyl]-5-nitro-2,3-pyridinedicarboxylate(30.9 g, 0,092 mol) is dissolved in (500 mL) tetrahydrofuran undernitrogen and 3.1 g of 10% palladium on carbon is added all at once tothe red solution. Sodium hypophosphite (121.00 g, 1.375 mol) dissolvedin water is then added dropwise to the solution over three hours andhydrogen gas evolution is noted during this time. Ether (500 mL) isadded to the pale yellow reaction mixture and the two phase mixture isfiltered through a pad of celite. The ethereal layer is separated andconcentrated in vacuo to give the product as a pale yellow solid in 987°yield, having a melting point 154°-158° C.

Similarly, diethyl1-hydroxy-2-methylpyrrolo[3,2-b]pyridine-5,6-dicarboxylate is preparedin 95% yield, having a melting point 178°-179.5° C., from6-[2(dimethylamino)propenyl]-5-nitro-2,3-pyridinedicarboxylate.

Diethyl 1-hydroxy-2-phenylpyrrolo[3,2-b]pyridine-5,6-dicarboxylate,having a melting point of 179°-182.5° C., is also prepared from6-[2-(dimethylamino)styryl]-5-nitro-2,3-pyridinedicarboxylate using theabove procedure. The pale yellow solid product is purified bychromatography and recrystallized from ethyl acetate.

EXAMPLE 58 Preparation of diethyl1-methoxypyrrolo[3,2-b]pyridine-5,6-dicarboxylate and diethyl1-methylpyrrolo[3,2-b]pyridine-5,6-dicarboxylate ##STR146##

Diethyl 1-hydroxypyrrolo[3,2-b]pyridine-5,6-dicarboxylate (25.2 g, 0.091mol) is dissolved in 100 mL dimethylformamide and, the solution cooledto 0° C. under nitrogen. Potassium t-butoxide (20.42 g, 0.182 mol) isadded over 15 minutes so that the reaction temperature is no higher than15° C. The red solution is stirred for 15 minutes and methyl iodide(11.33 mL, 0.182 mol) is then added dropwise over 15 minutes, so thatthe reaction temperature is no higher than 15° C. The mixture is allowedto warm to room temperature then stirred for 16 hours. The resultingsuspension is filtered and the mother liquors concentrated in vacuo. Theresulting oil is partitioned between ethyl acetate and water (pH 8), andthe organic layer separated and concentrated in vacuo. The resultingyellow oil, containing a mixture of diethyl1-methoxypyrrolo[3,2-b]pyridine-5,6-dicarboxylate, is chromatographedusing 9:1 hexane/ethyl acetate and increasing the polarity to 2:1hexane/ethyl acetate. The fractions containing the methoxy product(confirmed by NMR) are combined and concentrated in vacuo to give 53.2%yield of a pale yellow solid, melting point 87.5°-89° C. The fractionscontaining the methyl product are combined and concentrated in vacuo togive 23.8% yield of a tan solid, melting point 97°-100° C.

EXAMPLE 59 Preparation of diethyl1-methoxy-2-phenylpyrrolo[3.2-b]-pyridine-5,6-dicarboxylate ##STR147##

1-Hydroxy-2-phenylpyrrolo[3,2-b]pyridine-5,6-dicarboxylate (1.3 g,0.0037 mol), is dissolved in 50 mL dimethylformamide and cooled to -30°C. under nitrogen. Potassium t-butoxide (0.85 g, 0.007 mol) is addedover ten minutes so that the reaction temperature is no higher than -24°C. The red solution is stirred for five minutes and methyl iodide (0.87mL, 0.014 mol) is then added dropwise over five minutes so that thereaction temperature is no higher than -20° C. The mixture is thenallowed to warm to room temperature and stir for 16 hours. Thesuspension is concentrated in vacuo. The resulting oil is partitionedbetween ethyl acetate and water (pH 8). The organic layer is separatedand concentrated in vacuo The resulting yellow oily solid is flashchromatograpbed using 9:1 hexane/ethyl acetate. The product is obtainedas a pale yellow solid weighing 1.0 g (73.5% yield) having a meltingpoint 95°-96.5° C.

Similarly, diethyl1-methoxy-2-methylpyrrolo[3,2-b]pyridine-5,6-dicarboxylate is preparedfrom diethyl 1-hydroxy-2-methylpyrrolo[3,2-b]pyridine-5,6-dicarboxylatein 95% yield having melting point 94.5°-96.5° C.

EXAMPLE 60 Preparation of diethyl1-(allyloxy)pyrrolo[3,2-b]pyridine-5,6-dicarboxylate ##STR148##

Diethyl 1-hydroxypyrrolo[3,2-b]pyridine-5,6-dicarboxylate (6.2 g, 0.022mol) is dissolved in (200 mL) dry tetrahydrofuran and cooled to 0° C.under nitrogen. Sodium hydride (0.77 g, 0.033 mol) is added in portionsover ten minutes and the reaction is stirred for 30 minutes at 0° C.Allyl bromide (2.01 mL, 0.024 mol) is added all at once to thesuspension and the mixture allowed to warm to room temperature and thenstirred for 16 hours. The mixture is filtered and the filtrateconcentrated in vacuo. The resulting oil is chromatographed using 4:1hexanes/ethyl acetate and then increasing the polarity to 2:1hexanes/ethyl acetate to give the product as a yellow oil in 89% yield.

EXAMPLE 61 Preparation of diethyl1-(difluoromethoxy)pyrrolo[3.2-b]-pyridine-5,6-dicarboxylate and diethylpyrrolo[3,2-b]-pyridine-5,6-dicarboxylate ##STR149##

Sodium methoxide (8.1 g, 0.15 g) is added slowly over 15 minutes todiethyl 1-hydroxypyrrolo[3,2-b]pyridine-5,6-dicarboxylate (6.94 g, 0.025mol), suspended under nitrogen in 100 mL absolute ethanol at 0° C. Themixture is then heated to reflux and Freon 22 gas is bubbled through thereaction suspension for six hours. Additional sodium methoxide (8.1 g,0.15 mol), is added in portions at reflux and the Freon addition stoppedafter a total of eight hours. The reflux is continued for 16 hours.Additional sodium methoxide (8.1 g, 0.15 mol) is added and Freon 22 gasis again bubbled through the suspension for six hours at reflux.

The Freon gas addition is then stopped and the mixture is heated for 72hours at reflux. The mixture is cooled to room temperature and ethanolicHCl added until a pH 4-5 is achieved. The solid suspension is filteredand the filtrate concentrated in vacuo to a yellow oil which ischromatographed using 4:1 hexane/ethyl acetate, to give the titleproduct as a yellow oil, 16.2% yield. The major side product collectedis diethyl pyrrolo[3,2-b]pyridine-5,6-dicarboxylate in 52% yield as apale yellow solid, having a melting point 109°-111° C.

EXAMPLE 62 Preparation of diethyl1-methoxy-3-chloropyrrolo[3.2-b]-pyridine-5,6-dicarboxylate ##STR150##

Benzoyl peroxide (0.91 g, 0.037 mol) is added to diethyl1-methoxypyrrolo[3,2-b]pyridine-5,6-dicarboxylate (1.0 g, 0.003 mol)dissolved in (40 mL) carbon tetrachloride under a nitrogen atmosphereand the suspension stirred for ten minutes. N-Chlorosuccinimide (0.84 g,0.0063 mol) is then added and the reaction heated at 60° C. for fourhours. The mixtue is cooled to room temperature and the inorganics areremoved by filtration. The organic mother liquors are washed with waterand sodium bisulfate and concentrated in vacuo to an orange oil. The oilis flash chromatographed using hexanes and then 4:1 hexanes/ethylacetate, giving the title product as an off-white solid in 51% yield,having a melting point 146°-148° C.

The ethereal mother liquors are concentrated in vacuo and dissolved in(100 mL) acetic acid. Palladium on carbon (0.44 g, 5%) is added and themixture is shaken for 16 hours under 50 psi hydrogen in a parthydrogenator. The reaciton is stopped and the dark solution is filteredthrough a pad of celite and concentrated in vacuo. The resulting oil ischromatographed using 7:1 hexane/ethyl acetate and then 3:1 hexane/ethylacetate, to give the title product as a pale yellow solid in 31% yield,having a melting point 109°-111° C.

EXAMPLE 63 Preparation of diethylpyrrolo[3,2-b]pyridine-5,6-dicarboxylate ##STR151##

Diethyl 6-[2-(dimethylamino)vinyl]-5-nitro-2,3-pyridinedicarboxylate(20.0 g, 0.059 mol) is partially dissolved in 200 mL acetic acid andthen (0.6 g) 5% palladium on carbon is added all at once. The mixture isshaken for 16 hours under psi hydrogen in a Parr hydrogenator. Thereaction is stopped and the suspension is diluted with ethanol andfiltered through a pad of celite. The mother liquors are concentrated invacuo to a dark red oil. Trituration with ether gives the N-hydroxycompound as a white solid in 40% yield, having a melting point 154°-158°C.

The ethereal mother liquors are concentrated in vacuo and dissolved in100 mL acetic acid. Palladium on carbon (0.44 g, 5%) is added and theentire mixture is shaken for 16 hours in a Parr hydrogenator. Thereaction is stopped and the dark solution is filtered through a pad ofcelite and concentrated in vacuo. The resulting oil is gravitychromatographed using 7:1 hexane/ethyl acetate and increasing inpolarity to 3:1 hexane/ethyl acetate. A pale yellow solid is collected.Yield: 31%, melting point 109°-111° C.

EXAMPLE 64 Preparation of dimethoxy3-chloro-1-methyl-1H-pyrrolo[2,3-b]pyridine-5,6-dicarboxylate ##STR152##

To a solution of (1.74 g, 0.0070 mol) dimethoxymethyl-1H-pyrrolo[2,3-b]pyridine-5,6-dicarboxylate in 50 mL CCl₄ isadded a mixture of 0.98 g (0.0073 mol) N-chlorosuccinimide and 0.18 g(0.00073 mol) benzoyl peroxide. The resulting solution is stirred forfour hours at reflux and 15 hours at 60° C. The solution is cooled toroom temperature, diluted with 100 mL CH₂ Cl₂ and washed with 5% NA₂ S₂O₅. The aqueous layer is extracted with an additional 50 mL CH₂ Cl₂ andthe combined organic solutions are dried over MgSO₄ and concentratedunder vacuum. The crude product is chromatographed on 50 g silica using3:1 hexanes:ethyl acetate as eluant to afford 0.87 g (44%) ofdimethoxy-3-chloro-1-methyl-1H-pyrrolo[2,3-b]pyridine-5,6-dicarboxylateas a yellow solid, mp 129°-137° C.

EXAMPLE 65 Preparation of 1B-pyrazolo[3,4-b]quinoline ##STR153##

Hydrazine hydrate (10 g, 0.20 mol) is added dropwise to a suspension of2-iodoquinoline-3-carboxaldehyde ethylene ketal (65.5 g, 0.20mol), (O.Meth-Cohn, J. Chem. Soc., Perkin I, 2509 (1981), m.p. 104.5°-106.5° C.in methanol (250 mL) containing triethylamine 28 mL) at reflux. Afterrefluxing overnight additional hdyrazine hydrate (10 g) is added and themixture is stirred at reflux for another six and one-half hours.Concentrated hydrochloric acid (75 mL) is then added dropwise, while themixture is refluxing and the reaction continued for one hour. Thereaction mixture is cooled, poured onto ice and allowed to stand for twodays. A red solid is removed by filtration and the filtrate isconcentrated by rotary evaporation to remove methanol. The remainingsolution is adjusted to pH 9 with concentrated ammonium hydroxide andthe cream colored precipitate is filtered, washed with water and airdried. Recrystallization from ethanol gives an analytical sample,melting point 207°-208° C., calcd. for C₁₀ H₇ N₃ : C, 70.99; H, 4.17; N,24.84. Found: C, 70.82: H. 4.06; N, 24.18.

EXAMPLE 66 Preparation of 1H-pyrazolo[3,4-b]pyridine-2,3-dicarboxylicacid ##STR154##

Crude 1H-pyrazolo[3,4-b]quinoline is suspended in water (300 mL) andheated to 60° C. The heat source is removed and a total of 100 g ofpotassium permanganate (0.64 mol) is added in portions so as to maintainthe reaction temperature below 72° C. Additional water (100 mL) is addedafter addition of one-half of the permangate. Upon completion of theaddition the mixture begins to cool, and it is heated to 100° C. for 25minutes, then cooled to room temperature. The mixture is filteredthrough celite, and the solids washed with hot water (100 mL). Thefiltrate is acidified to pH 2 with concentrated hydrochloric acid andthe resulting solution is concentrated on the rotary evaporator to 75mL, and chilled in an ice bath. The solids which precipitate arefiltered off and dried in an oven at 50° C. overnight, giving 11 g.Recrystallization from 95% ethanol gives the pure product having mp270°-285° C. (slow dec).

EXAMPLE 67 Preparation of diethyl1H-pyrazolo[3,4-b]pyridine-5,6-dicarboxylate ##STR155##

A suspension of 1H-pyrazolo[3,4-b]pyridine-5,6-dicarboxylic acid (62 g)in 500 mL of an ethanol sulfuric acid mixture (10:1 by weight) is heatedat reflux for 16 hours. The suspension is cooled and filtered and thefiltrate concentrated in vacuo. Column chromatography usinghexanes/ethyl acetate (4:1) elution gives 4.0 g of the title product asan oil.

EXAMPLE 68 Preparation of diethyl1-methyl-1H-pyrazolo[3,4-b]pyridine-5,6-dicarboxylate and diethyl2-methyl-2H-pyrazolo-3,4-b]pyridine-5,6-dicarboxylate ##STR156##

To a solution of diethyl 1H-pyrazolo[3,4-b]pyridine-5,6-dicarboxylate(4.0 g, 0.015 mol) in THF (50 mL) at 5° C. is added a NaH (0.70 g of60%, 0.018 mol) dispersion in mineral oil. The mixture is stirred forten minutes and then methyl iodide (2.84 g, 0.020 mol) is added. Themixture is stirred overnight at room temperature, then concentrated invacuo to give a crude mixture of the isomers which are separated bycolumn chromatography (hexanes/ethyl acetate (4:1) elution), affording1.2 g (28.5%) of 1H-pyrazolo[3,4-b]pyridine-5,6-dicarboxylate as thefaster eluting product, and 2.6 g (61.8%) of the2H-pyrazolo[3,4-b]pyridine-5,6-dicarboxylate as the slower elutingproduct as oils.

EXAMPLE 69 Preparation of 3-hydroxytetrahydropyran ##STR157##

To 33.6 (0.4 mol) of Δ² -dihydropyran in 240 mL of tetrahydrofuran isadded 140 mL of 1.0M solution of borane in tetrahydrofuran (0.015 equiv.of hydride) at 0° to 5° C. The reaction mixture is stirred at thistemperature for three hours and then warmed to 25° C. and stirred for anadditional two hours. The organic borane is oxidized at 40° to 45° C. byadding 72 mL of 3N sodium hydroxide solution followed by dropwiseaddition of 48 mL of 30% hydrogen peroxide. After the reaction mixtureis stirred for one to two hours at room temperature, a saturated sodiumchloride solution is added and the phases are separated. The aqueousphase is extracted with 5×100 mL portions of ether and the combinedorganic layers are dried over anhydrous sodium sulfate. The solvent isremoved under reduced pressure giving the product as a colorless oil,38.3 g, yield 92.5% which when analyzed by gas chromatography gives asingle peak, bp 40°-50° C.

EXAMPLE 70 Preparation of tetrahydropyranone-3 ##STR158##

Jones reagent is prepared by adding in portions 74.2 g (0.249 mol) ofpotassium dichromate dihydrate to a cooled solution of 87.10 g (0.88mol) of concentrated sulfuric acid in 125 mL of water. This reagent isadded dropwise to a cold solution (ice-bath) of (38.28 g, 0.375 mol)3-hydroxytetrahydropyran, in 125 mL of ether over a period of threehours. The mixture is stirred for three hours at 0° C., after whichanother 125 mL of ether is added and the mixture is warmed to roomtemperature and stirred overnight. Ice cold water 100 mL is added andthe layers are separated. The aqueous layer is extracted with 4×100 mLportions of ether, the organic phases are combined and dried overanhydrous magnesium sulfate. The solvent is removed under reducedpressure giving the product as a light yellow oil, 26.37 g, 70% yield.

EXAMPLE 71 Preparation of morpholine, 4-(3,4-dihydro-2H-pyran-5-yl)##STR159##

Tetrahydropyranone-3, (25.38 g, 0,253 mol) is refluxed in 75 mL ofbenzene overnight with 33..0 g (0.38 mol, 1.5 equiv.) of morpholine anda catalytic amount of p-toluene sulfonic acid until the theoreticalamount of water (4.7 mL) is separated within a Dean-Stark trap. Thebenzene is removed on a rotary flash evaporator and the product isolatedas a clear red oil in 95% yield.

EXAMPLE 72 Preparation of 2H-pyrano[3,2-b]pyridine-6,7-dicarboxylicacid, 3,4-dihydro-diethyl ester ##STR160##

An ethanol solution solution (100 mL) containing diethyl ethoxymethyleneoxalacetate (50.2 g, 0.205 mol) is added to a stirred ethanol (200 mL)solution containing the enamine (23.2 g, 0.137 mol) prepared in Example53 at 0° C. and the mixture stirred for two hours. The reaction mixtureis allowed to warm to room temperature and ammonium acetate (42.2 g) isadded. After stirring overnight at room temperature, additional ammoniumacetate (21.1 g) is added and the mixture is heated at 70° C. for twohours and is then allowed to cool to room temperature. Water (250 mL) isadded and the resulting mixture extracted with methylene chloride (5×150mL). The organic layer is separated, dried over anhydrous Na₂ SO₄,filtered and the solvent removed under reduced pressure. The resultingoily residue is purified by column chromatography on silica gel with amethylene chloride ethyl acetate mixture (99:1) as the eluant to givethe title product as a yellow oil in 17% yield.

EXAMPLE 73 Preparation ofdiethyl-7,8-dihydro-6H-thiopyrano[3,2-b]pyridine-2,3-dicarboxylate##STR161##

Diethyl ethoxymethylene oxalacetate (28.9 g, 1.1 equiv.) is addedslowly, over ten minutes to a solution of4-(5,6-dihydro-4H-thiopyran-3-yl)morpholine (Hirsh and Wang, Syn Comm.12, 333 (1982) (assumed quantitative yield of morpholino enamine; 0.107mol; one equiv.) in 300 mL of absolute ethanol cooled to 0° C. (icebath). The mixture is stirred for one hour whereupon ammonium acetate(21.5 g: 3 equiv.) is added and the mixture heated at reflux and stirredan additional three hours. The mixture is cooled and the solvent removedin vacuo. The red syrup is flash chromatographed eluting with hexanesand gradually increasing eluant polarity to 15% ethyl acetate/hexanes togive 7.81 g (25%) of a clear yellow oil.

EXAMPLE 74 Preparation of methyl 2-aminopyrazine,3-carboxylate##STR162##

3-Aminopyrazine-2-carboxylic acid (55.5 g, 0.4 mol) is suspended in 400mL of methanol, cooled in an ice bath and concentrated sulfuric acid (80mL) is gradually added with stirring and stirring then continued for 48hours at room temperature. The resulting dark brown solution is pouredinto 700 mL of water containing sodium bicarbonate (160 g). The browncrystalline solid which precipitates is collected and dried. The crudeproduct is purified by recrystallization from water to yield the productas yellow needles in 63% yield, melting point 169°-170° C.

EXAMPLE 75 Preparation of pyrazine methanol, 3-amino ##STR163##

Lithium aluminum hydride (2.4 g, 0.003 mol) is added in increments to astirred suspension of methyl 3-aminopyrazine-2-carboxylate (9.0 g, 0.059mol) in 600 mL of tetrahydrofuran, in a 2 liter 4-neck flask fitted witha N₂ -inlet tube, thermometer, and a condenser over a period of 30minutes. After the reaction mixture is stirred at room temperature foran additional hour, water 20 mL is added with caution and the solidswhich form are filtered off. The filtrate is dried over anhydrous sodiumsulphate, and filtered. The solvent is removed under reduced pressure,giving a yellow semi-solid residue, 6.5 g, 88% yield. A portion of thissolid is extracted with methylene chloride, which gives a crystallinesolid, melting point 112°-119° C.

EXAMPLE 76 Preparation of 3-aminopyrazinecarboxaldehyde ##STR164##

A suspension of 3-aminopyrazine methanol, 6.3 g (0.05 mol) and manganesedioxide (38.0 g) in 400 mL of chloroform is stirred at room temperaturefor two hours and the resulting solid is filtered off. The filtrate isevaporated to dryness which gives the desired product as a yellowcrystalline solid, (5.00g, 82% yield) having a melting point 110°-114°C.

EXAMPLE 77 Pyrido[2,3-b]pyrazine-6,7-dicarboxylic acid, diethyl ester##STR165##

Diethyl oxalacetate, (4.7 g, 0.025 mol) and piperidine (1.66 g, 1.93 mL)are added to 3-aminopyrazine-2-carboxaldehyde (2.4 g, 0.0195 mol)dissolved in 250 mL of toluene. After the reaction mixture is refluxedfor two hours, the toluene is removed under reduced pressure to give adark red oily residue. The product is purified by column chromatographyon silica gel (hexane:EtOAc, 4:1), affording 3.1 g (58% yield), of thecrude desired product. Crystallization from ether-hexane (4:1) givesanalytically pure compound 1.5 g (28%) having a melting point 83°-85° C.

EXAMPLE 78 Preparation of 4-pentynyl methanesulfonate ##STR166##

To pentyne-4-ol (Farchan Chemical Co) (42.0 g: 0.5 mols) in 500 mL etherat -5° C. (dry ice bath) is added in a rapid dropwise fashiontriethylamine (104.8 mL; 0.75 mols) diluted with 100 mL ether. Whilemaintaining the temperature at or below 15° C. throughout, methanesulfonyl chloride, (94.2 mL; 0.70 mols) diluted with 100 mL ether, isadded dropwise over 45 minutes. The thick suspension is stirred anadditional 30 minutes, after which the precipitate is filtered. Thefilter cake is washed with ether and the combined ether layers washedtwice with water, then once with brine. The ether layer is then driedover anhydrous magnesium sulfate and solvent removed under reducedpressure to yield the product as a pale yellow oil; yield 64 g (79%),which is used in the next step without further purification.

A small sample is purified by bulb-to-bulb distillation, boiling point70°-85° C., 0.15 mm Hg).

EXAMPLE 79 Preparation of S-(4-pentynyl)thiosemicarbazide, 1:1 salt withmethanesulfonic acid ##STR167##

Thiosemicarbazide (27.3 g; 0.3 mols) is suspended in 200 mL ethanol andbrought to reflux. Crude 4-pentynylmethanesulfonate (51.0 g; 0.32 mols),diluted with 50 mL ethanol, is added dropwise to the suspension over 40minutes. The solids all dissolve after a few hours and refluxing itcontinued for 48 hours. Removal of solvent under reduced pressure yieldsthe product as a thick amber oil which is washed three times with hotether. The crude product is used in the next step without furtherpurification.

EXAMPLE 80 Preparation of dimethyl 2,3-dioxosuccinate ##STR168##

A suspension of 250 g of 2,3-dihydroxytartaric acid, disodium salthydrate (Aldrich) in one liter of methanol is saturated at 0 to 10° C.with gaseous HCl and allowed to stand for one week at 5° C. Solids areremoved by filtration and the solvent is then removed to give a thickyellow oil. Vacuum distillation of the oil gives the desired productboiling point 92°-101° C., 2.3-2.5 mm, suitable for use in the followingsteps.

EXAMPLE 81 Preparation of dimethyl2H-dihydrothiopyrano[2,3-b]pyridine-6,7-dicarboxylate ##STR169##

A mixture of S-(4-pentynyl)thiosemicarbazide methanesulfonic acid salt(25.0 g; 0.1 mols) in chlorobenzene (175 mL) is cooled to -5° C. in anice-acetone bath under a nitrogen purge. Triethylamine (14.0 mL; 0.1mol) in chlorobenzene (25 mL) is added dropwise over 30 minutes and themixture is stirred another 20 minutes. A solution of dimethyl2,3-dioxosuccinate (26.0 g; 0.1 mols, assuming 65% purity) inchlorobenzene (50 mL) is added dropwise over 30 minutes, causing most ofthe thick oil to dissolve. The ice bath is removed and the solution isbrought to reflux. After refluxing for 28 hours, the solution is cooled,and solids removed by filtration. The filtrate is concentrated underreduced pressure and the residue partitioned between water and ethylacetate. The water layer is washed with fresh ethyl acetate, and thecombined organics are washed with saturated NaCl and dried over MgSO₄.The solvent is removed under reduced pressure, and the residual oilchromatographed (waters prep 500 HPLC; 3% ethyl acetate in methylenechloride). The fractions containing the desired product are combined andsolvent is removed under reduced pressure. The product is obtained as alight beige solid (7.5 g) which is recrystallized from 2-propanol toobtain a crystalline off-white solid (6.4 g), homogeneous by TLCmp=82°-85° C.

EXAMPLE 82 Preparation of6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-1H-1-methyl-pyrazolo-[3,4-b]pyridine-5-carboxylic acid ##STR170##

Diethyl-1-methyl-1H-pyrazolo[3,4-b]pyridine-5,6-dicarboxylate (24 g) in200 mL of 1:1 ethanol-water is heated at reflux overnight, thenconcentrated on a rotary evaporator. The residue is acidified to pH 1with 6N HCl, cooled and filtered to remove the solid diacid product,which is then washed with cold water and air dried. The yielde is (32%)of crude diacid mp 228°-229° C. (dec).

The diacid (9.g) in acetic anhydride (40 mL) is stirred at 85°-90° C.for two hours. The reaction mixture is filtered while hot and thefiltrate is concentrated under reduced pressure to yield the crudeanhydride as a gum. The product is dissolved in tetrahydrofuran (50 mL),2-amino-2,3-dimethylbutyramide is then added and the mixture is stirredwhile heating to 40° C. for one andone-half hours and then at reflux for16 hours. Upon completion of the reaction, the mixture is cooled to roomtemperature and concentrated in vacuo. The residue is dissolved inaqueous NaOH (10 g/100 mL), 100 mL) and the resulting solution isstirred at 75°-85° C. for four hours. After cooling to room temperaturethe reaction mixture is cooled to 10° C. and acidified to pH 2 withconcentrated hydrochloric acid.

The resulting precipitate is collected by filtration, dried and purifiedby column chromatography on silica gel utilizing ethyl acetate-ethanolon the eluant to give the title product as a tan solid having a meltingpoint 239°-243° C.

EXAMPLE 83 Preparation of7-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-4H-2,3-dihydro-4-methylpyrano[2,3-b]pyridine-6-carboxylicacid ##STR171##

The crude 2H-pyranopyridine imidazoline carboxylic acid is suspended in10 mL of water and to this suspension is added 10 mL of 15% aqueouspotassium carbonate solution. The material dissolves to give a clearyellow-brown solution. Ethanol, 95% (40 mL) is added to the solutionslowly, so that the layers do not separate. 5%/Pd/C, 100 mg is added tothis solution and the mixture is agitated on a Parr hydrogenatorovernight. The mixture was filtered and evaporated to dryness. Theresidue is taken in 50 mL of water and washed with 2×25 mL portions ofmethylene chloride which are discarded. The aqueous layer is made acidicwith concentrated HCl to pH 1 while cooling in an ice bath and extractedwith 5×50 mL portions of methylene chloride.

The combined methylene chloride extracts are dried over anhydrous sodiumsulfate, filtered and the solvent is removed under reduced pressure.This gives the product as shiny, slightly, yellowish fluffy said, mp95°-99° C.

Utilizing the procedure of Example 43, 44, 45, 82 and 83, andsubstituting the appropriate fused heteropyridine dicarboxylic acid andamino amide or amino thiomide yields the (imidazolin-2-yl)fusedheteropyridine compounds listed in Table III below.

                  TABLE III                                                       ______________________________________                                        (Imidazolin-2-yl)fused heteropyridine carboxylic acids                         ##STR172##                                                                   Fused heteropyridine      mp°C.                                        ______________________________________                                         ##STR173##               223.0-224.0                                          ##STR174##               247.0-250.0                                          ##STR175##               226.0-227.0                                          ##STR176##               239.0-243.0                                          ##STR177##               180.0-185.0                                          ##STR178##               282.0-283.0                                          ##STR179##               >350                                                 ##STR180##               170.0-173.0                                          ##STR181##               236.0- 239.0                                         ##STR182##               199.0-201.0                                          ##STR183##               220.0-222.0                                          ##STR184##               164.0-166.0                                          ##STR185##               155.0-167.0 (dec)                                    ##STR186##               188.0-190.0                                          ##STR187##               225.5-227.0                                          ##STR188##                95.0-99.0                                           ##STR189##               215.5-218.0                                          ##STR190##               264.0-266.0                                          ##STR191##               215.0-221.0                                          ##STR192##               178.0-179.0                                          ##STR193##               230.0-233.0                                          ##STR194##               --                                                   ##STR195##               195.0-197.0                                          ##STR196##               256.0-258.0                                          ##STR197##               248.0-250.0                                          ##STR198##               198.0-201.0                                          ##STR199##               147.0-150.0                                          ##STR200##               247.0-252.0                                          ##STR201##               134-138                                              ##STR202##               --                                                   ##STR203##               166-169                                              ##STR204##               --                                                   ##STR205##               200.0-204.0                                          ##STR206##               209.0-210.0                                          ##STR207##               272.0-284.0                                          ##STR208##               257.0-262.0                                          ##STR209##               208.0-210.0                                          ##STR210##               264.0 (dec)                                          ##STR211##               --                                                   ##STR212##               --                                                   ##STR213##               --                                                   ##STR214##               --                                                   ##STR215##               --                                                   ##STR216##               --                                                   ##STR217##               --                                                  ______________________________________                                    

EXAMPLE 84 Preparation of2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-8-oxide-1,8-naphthyridine-3-carboxylicacid ##STR218##

m-Chloroperbenzoic acid (37.70 g) is added in one portion of2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-1,8-naphthyridine-3-carboxylicacid (27.32 g, 0.087 mol, 1 equiv) suspended in 465 mL methylenechloride and 300 mL methanol under N₂ and the mixture is stirred at roomtemperature for 15 hours. The suspension is filtered and the filtrateconcentrated to a yellow solid which is recrystallized frommethanol/ether, yielding the product as a dark yellow solid, (10.84 g,37.7% yield, having a melting point 219°-221° C. (dec).

EXAMPLE 85 Preparation of methyl7-chloro-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-1,8-naphthylidine-3-carboxylate##STR219##

Methyl2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-8-oxide-1,8-naphthylidine-3-carboxylate(4.11 g, 0.012 mol) is suspended under N₂ in 80 mL phosphorousoxychloride and heated to 53° C. for one hour. The solution is strippedto an oil, taken up in ethyl acetate and washed with water, a 10% sodiumcarbonate solution and brine. The organic layer is dried over Na₂ SO₄,filtered and concentrated to a brown solid. The solid is purified bychromatography on silica gel, using methylene chloride and then 7:3methylene chloride/ethyl acetate. The fractions containing the desiredproduct are combined and the solvent removed yielding the title productas an off-white solid (1.77 g, 40.9%) having a melting point 161°-162°C.

EXAMPLE 86 Preparation of2-isopropyl-2-methyl-7,8-dihydro-5H-pyrano[4,3-b]imidazo[2',1':5,1]pyrrolo[3,4-e]pyridine-3-(3H),0dione ##STR220##

Dicyclohexylcarbodiimide (2.94 g) is added to a suspension of theimidazolinone (1.2 g) in methylene chloride (100 mL). After stirring forthree days at room temperature, the mixture is filtered to remove awhite solid bi-product and the filtrate is concentrated to give an oilysolid which contains the product. Chromatography on silica gel using 9:1methylene chloride:methanol gives 0.92 g of the desired product.

Using essentially the same procedure and using the appropriatelysubstituted imidazolinyl heteropyridine carboxylic acid, gives othersubstituted imidazopyrroloheteropyridine-3,5-diones or 3-thione-5-ones.

EXAMPLE 87 Preparation of3-isopropyl-3-methyl-7,8-dihydro-5H-pyrano[4,3-b]imidazo[2', 1':5,1]pyrrolo[3,4-e-]pyridine-2(2H), 5-dione ##STR221##

To a suspension of6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-7,8-dihydro-5H-pyrano[4,3-b]pyridine-carboxylicacid (1.17 g, 3.75 mmol) in 20 mL dimethoxyethane (DME) is added 1.0 mLacetic anhydride and 0.5 mL pyridine. After stirring 24 hours at roomtemperature, the solids are filtered and washed with ether and themother liquor is concentrated by adding xylene to remove pyridine. Theresidue is triturated with ether and combined with the first crop togive 1.10 g (100% of product as a solid.

Using essentially the same procedure and using the appropriatelysubstituted imidazolinyl heteropyridine carboxylic acid, gives othersubstituted imidazopyrroloheteropyridine-2,5-diones, or 2-thione-5-ones.

EXAMPLE 88 Preparation of methyl2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carboxylate##STR222##

To a suspension of 2.0 g2-isopropyl-2-methyl-7,8-dihydro-5H-pyrano[4,3-b ]imidazo[2', 1':5,1]pyrrolo[3,4-e]pyridine-2(2H), 5-dione in 100 mL absolute methyl alcoholis added 0.2 g of sodium methoxide over a five minute period. Thetemperature of the reaction is kept below 30° C. by immersion in an icebath. After the addition was complete, the reaction mixture was kept atroom temperature for 24 hours and acidified with three drops of aceticacid, and stripped in vacuo. The product was chromatographed on silicagel using methylene chloride-ethyl acetate to give 1.55 g of the esterproduct. After recrystallization from methylene chloride-hexane, it hadmp 208°-220° C.

Utilizing essentially the same procedure and using the appropriatelysubstituted fused hereto imidazopyrrolopyridine-2,5-dione and alcohol,gives the substituted (imidazolin-2-yl)fused heteropyridine carboxylatesin Table IV below.

                  TABLE IV                                                        ______________________________________                                        (Imidazolin-2-yl)fused heteropyridine carboxylates                             ##STR223##                                                                   Fused                                                                         heteropyridine   R.sub.8       mp °C.                                  ______________________________________                                         ##STR224##      CH.sub.3      200.0-210.0 (dec)                               ##STR225##      CH.sub.3      208.0-220.0 (dec)                               ##STR226##                                                                                     ##STR227##   197.0-206.0 (dec)                               ##STR228##      CH.sub.2 CCH  --                                              ##STR229##                                                                                     ##STR230##   --                                              ##STR231##      CH.sub.3      --                                              ##STR232##      CH.sub.2 CCH  --                                             ______________________________________                                    

EXAMPLE 89 Preparation of methyl2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carboxylate##STR233##

A solution of the ester in 50 mL absolute methanol is acidified to pH 3with methanolic HCl. At 0° C. is added, all at once, 0.1 g sodiumcyanoborohydride and the mixture stirred overnight at room temperature.The pH is again adjusted to 3 and an additional 0.1 g sodiumcyanoborohydride is added. After 16 hours, the mixture is quenched indilute HCl, then neutralized to pH 7 with carbonate and extracted withmethylene chloride. The crude extract is stripped to a solid productwhich is a mixture of two isomers. These are separated by flashChromatography on silica using ethyl acetate-methylene chloride. About0.7 g of the cis or slower-moving isomer and 0.3 g of the faster-movingtrans isomer are obtained. ##STR234##

The ester aldehyde (1.0 g) and the aminoamide are dissolved in 50 mLtoluene acid 0.10 g, E-toluene-sulfonic acid added. The mixture isrefluxed six hours under nitrogen and the water separated using aDean-Stark trap. It is then filtered while hot, cooled and thenconcentrated on a rotary evaporator. Extraction with hexane/ether gives,after cooling a white solid which is chromatographed as in Method A togive both cis- and trans-isomers.

Using essentially the same methods as A and B above, otherimidazolidinyl fused heteropyridine carboxylates may be prepared.

EXAMPLE 90 Preparation of3-isopropyl-3-methyl-1,7,8,9-b-tetrabydro-5H-pyrano[4,3-b]imidazo [2',1': 5,1]pyrrolo[3,4-e]-pyridine 2(2H), 5-dione ##STR235##

The acid (1.0 g) is suspended in 25 mL acetonitrile and 0.5 mL aceticanhydride and 0.5 mL pyridine are added. After 18 hours at roomtemperature, 20 mL ether is added and the mixture is filtered to obtainthe product as a white solid.

Using essentially the same procedure, otherimidazopyrroloheteropyridine-2,5-diones may be prepared.

EXAMPLE 91 Preparation of2-(4-isopropyl-4-methyl-5-oxo-2-imidazolidinyl)-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carboxylicacid ##STR236##

The ester (1.2 g) is stirred for 18 hours at room temperature in 75 mLdioxane containing 2 mL water and 0.5 mL 85% potassium hydroxide. Themixture is then acidified with methanolic HCl, filtered and the filtratestripped and triturated with ether to give a white solid product.

Using essentially the same procedure, other imidazolidinylheteropyridinecarboxylic acids may be prepared.

EXAMPLE 92 Preparation of diethyl4-methyl-2-H-pyrano[2,3-b]pyridine-6,7-dicarboxylate ##STR237##

The 3,4-dihydro-4-oxo-pyrano [2,3-b ]pyridine diester (10.0 g, 0.34 mL)is dissolved in 150 mL ether and chilled to 0°, and methylmagnesiumbromide is added dropwise over one hour. The reaction is then allowed towarm to room temperature, stand one hour, and is then poured onto icewater containing ammonium chloride. The organic layer is removed, driedover MgSO₄ and stripped to give the oily intermediate. This4-methyl-4-hydroxy compound (5.0 g, 48%) is immediately redissolved in100 mL toluene, 4.0 g or p-toluenesulfonic acid is added, and themixture is heated to reflux for one hour. It is then cooled and thetoluene is removed in vacuo. The residue is treated with dilute sodiumbicarbonate solution and extracted with methylene chloride. Themethylene chloride solution is dried over MgSO₄, filtered andconcentrated to give, after silica gel chromatography, the4-methyl-pyrano[2,3-b]pyridine diester as an oil (2.1 g, 44%).

EXAMPLE 93 Preparation of methyl2-(1-acetyl-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-7,8-dihydro-5H-pyrano[4,3-b]pyridine-3-carboxylate##STR238##

The pyranopyridine carboxylate prepared in example 88 (1.0 g isdissolved in methylene chloride (50 mL) and 1 mL triethylamine is added.The mixture is chilled in an ice bath while acetyl chloride is added(0.25 g) and then stirred for 2 h and allowed to reach room temperature.The mixture is filtered, the solvent is stripped and the residue istaken up in methylene chloride and ammonium chloride solution. Theorganic layer is separated, washed with brine, dried over anhydrousmagnesium sulfate and concentrated to the crude product. Furtherpurification by silica gel chromatography, eluting with methylenechloride-ethyl acetate 9:1 gives the desired 1-acetyl compound as themajor product and the 3-acetyl compound as a by-product. The twomaterials are distinguishable by their infrared spectrum.

EXAMPLE 94 Preparation of6-(1-acetyl-4-isopropyl-4-methyl-5-oxo72-imidazolin-2-yl)-4H-2,3-dihydro-pyrano[2,3-b]pyridinecarboxylic acid ##STR239##

The benzylester is dissolved in 50 mL 955 ethanol and to it is added0.100 g 10% Palladium on charcoal catalyst. The material is hydrogenatedat atmospheric pressure for 6 h and then the solution is filtered,concentrated to give 0.6 g product. Using this same procedure, otherN-acylated and N-sulfonated imidazolinone heteropyridine carboxylicacids are prepared.

EXAMPLE 95

Utilizing the procedures of example 45 and substituting the appropriateheterofused pyridine dicarboxylic acid anhydride and aminoamide orthioamide, other acid diamides and acid amide thioamides of thestructures described in Table V below may be prepared.

                  TABLE V                                                         ______________________________________                                        (1-Carbamoyl and 1-thiocarbamoyl-1,2-dialkyl) carbamoyl                       heteropyridine carboxylic acids                                                ##STR240##                                                                   Heteropyridine  W      R.sub.1 R.sub.2 mp °C.                          ______________________________________                                         ##STR241##     S      CH.sub.3                                                                              CH(CH.sub.3).sub.2                              ##STR242##     S      CH.sub.3                                                                              CH(CH.sub.3).sub.2                              ##STR243##     S      CH.sub.3                                                                              CH(CH.sub.3).sub.2                              ##STR244##     S      CH.sub.3                                                                              CH(CH.sub.3).sub.2                              ##STR245##     S      CH.sub.3                                                                              CH(CH.sub.3).sub.2                              ##STR246##     O      CH.sub.3                                                                              C.sub.2 H.sub.5                                 ##STR247##     O      CH.sub.3                                                                              C.sub.2 H.sub.5                                 ##STR248##     O      CH.sub.3                                                                              cyclo-C.sub.3 H.sub.5                           ##STR249##     O      CH.sub.3                                                                              t-C.sub.4 H.sub.9                               ##STR250##     O      CH.sub.3                                                                              n-C.sub.3 H.sub.7                               ##STR251##     O      C.sub.2 H.sub.5                                                                       C.sub.2 H.sub.5                                ______________________________________                                    

EXAMPLE 96

Utilizing the procedures of examples 43, 44, 45, 82, 83, 86, 87, 88, 93and 94, other (imidazolin-2-yl) fused heteropyridine compounds areprepared and are listed in Table VI.

                                      TABLE VI                                    __________________________________________________________________________    (Imidazolin-2-yl) fused heteropyridine compounds                               ##STR252##                                                                   Fused                                                                         Heteropyridine                                                                              B          W R.sub.1                                                                            R.sub.2                                                                              R.sub.8 mp °C.                  __________________________________________________________________________     ##STR253##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR254##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H       221-222                         ##STR255##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR256##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR257##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR258##   H          O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 CH.sub.2 OCH.sub.3                                                           152-154                         ##STR259##   H          O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                                                              94 (dec.)                       ##STR260##   H          O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 C.sub.6 H.sub.5                                                              81-82                           ##STR261##   H          O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 CH.sub.2 OCH.sub.3                                                           110-112                         ##STR262##   H          O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                                                              173-174                         ##STR263##   H          O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 CH.sub.2 OCH.sub.3                                                           164-167                         ##STR264##   H          O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                                                              142-144                         ##STR265##   H          O CH.sub.3                                                                           C.sub.2 H.sub.5                                                                      H                                       ##STR266##   H          O CH.sub.3                                                                           C.sub.2 H.sub.5                                                                      H                                       ##STR267##   H          O CH.sub.3                                                                           cyclo-C.sub.3 H.sub.5                                                                H                                       ##STR268##   H          O CH.sub.3                                                                           t-C.sub.4 H.sub.9                                                                    H                                       ##STR269##   H          O CH.sub.3                                                                           n-C.sub.3 H.sub.7                                                                    H                                       ##STR270##   H          O C.sub.2 H.sub.5                                                                    C.sub.2 H.sub.5                                                                      H                                       ##STR271##   H          O (CH.sub.2).sub.4 CH(CH.sub.3)                                                             H                                       ##STR272##   COCH.sub.3 O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR273##   COCH.sub.3 O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR274##   COCH.sub.3 S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR275##   COCH.sub.3 O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR276##   SO.sub.2 C.sub.6 H.sub.4 CH.sub.3 P                                                      O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR277##   SO.sub.2 C.sub.6 H.sub.4 CH.sub.3 P                                                      O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR278##   SO.sub.2 C.sub.6 H.sub.4 CH.sub.3 P                                                      O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR279##                                                                                  ##STR280##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR281##                                                                                  ##STR282##                                                                              S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR283##   SO.sub.2 C.sub.6 H.sub.4 CH.sub.3 P                                                      O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   H                                       ##STR284##                                                                                  ##STR285##                                                                              O C.sub.2 H.sub.5                                                                    C.sub.2 H.sub.5                                                                      H                                       ##STR286##                                                                                  ##STR287##                                                                              O CH.sub.3                                                                           cyclo-C.sub.3 H.sub.5                                                                H                                       ##STR288##                                                                                  ##STR289##                                                                              O (CH.sub.2).sub.4 CH(CH.sub.3)                                                             H                                       ##STR290##                                                                                  ##STR291##                                                                              S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR292##                                                                                  ##STR293##                                                                              S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR294##                                                                                  ##STR295##                                                                              S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR296##                                                                                  ##STR297##                                                                              S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR298##                                                                                  ##STR299##                                                                              S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR300##   H          O CH.sub.3                                                                           cyclo-C.sub.3 H.sub.5                                                                CH.sub.3                                ##STR301##   H          O C.sub.2 H.sub.5                                                                    C.sub.2 H.sub.5                                                                      CH.sub.3                                ##STR302##   H          O (CH.sub.2).sub.4 CH(CH.sub.3).sub.3                                                       CH.sub.3                                ##STR303##                                                                                  ##STR304##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR305##   SO.sub.2 CH.sub.3                                                                        O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR306##   SO.sub.2 C.sub.6 H.sub.4 CH.sub.3 P                                                      O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR307##                                                                                  ##STR308##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR309##                                                                                  ##STR310##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 C.sub.6 H.sub.5                ##STR311##   SO.sub.2 C.sub.6 H.sub.4 CH.sub.3 P                                                      O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 C.sub.6 H.sub.5                ##STR312##                                                                                  ##STR313##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR314##                                                                                  ##STR315##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR316##                                                                                  ##STR317##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR318##                                                                                  ##STR319##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR320##                                                                                  ##STR321##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 C.sub.6 H.sub.5                ##STR322##                                                                                  ##STR323##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 C.sub.6 H.sub.5                ##STR324##                                                                                  ##STR325##                                                                              O CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.2 C.sub.6 H.sub.5                ##STR326##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub. 2                                                                  CH.sub.3                                ##STR327##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR328##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                                                              168-171                         ##STR329##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                                ##STR330##   H          S CH.sub.3                                                                           CH(CH.sub.3).sub.2                                                                   CH.sub.3                               __________________________________________________________________________

EXAMPLE 97

Utilizing the procedure of example 86, otherimidazopyrroloheteropyridine-3,5-diones are prepared and are listed inTable VII.

                                      TABLE VII                                   __________________________________________________________________________    Imidazopyrroloheteropyridine-3,5-diones                                        ##STR331##                                                                   Fused                                                                         Heteropyridine                                                                              W  R.sub.1                                                                             R.sub.2   mp °C.                                __________________________________________________________________________     ##STR332##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR333##   S  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR334##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR335##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR336##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                                                      228-236                                       ##STR337##   O  CH.sub.3                                                                            C.sub.2 H.sub.5                                         ##STR338##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                                                      180-183                                       ##STR339##   O  C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                         ##STR340##   O  CH.sub.3                                                                            cyclo-C.sub.3 H.sub.5                                   ##STR341##   O  CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH(CH.sub.3)             __________________________________________________________________________

EXAMPLE 98

Utilizing the procedure of example 87, otherimidazopyrroloheteropyridine-2,5-diones andimidazopyrroloheteropyridine-2-thione-5-ones are prepared and are listedin Table VIII.

                                      TABLE VIII                                  __________________________________________________________________________    Imidazopyrroloheteropyridine-2,5-diones (-2-thione-5-ones)                     ##STR342##                                                                   Fused                                                                         Heteropyridine                                                                              W  R.sub.1                                                                             R.sub.2   mp °C.                                __________________________________________________________________________     ##STR343##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR344##   O  CH.sub.3                                                                            CH(CH.sub. 3).sub.2                                     ##STR345##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR346##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR347##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR348##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR349##   S  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR350##   S  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR351##   S  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR352##   S  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR353##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR354##   O  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR355##   S  CH.sub.3                                                                            CH(CH.sub.3).sub.2                                      ##STR356##   O  CH.sub.3                                                                            cyclo-C.sub.3 H.sub.5                                   ##STR357##   O  C.sub.2 H.sub.5                                                                     C.sub.2 H.sub.5                                         ##STR358##   O  CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH(CH.sub.3)             __________________________________________________________________________

EXAMPLE 99

Utilizing the procedure of example 89, other imidazolidinyl fusedheteropyridine carboxylates and carboxylic acids are prepared and arelisted in Table IX.

                                      TABLE IX                                    __________________________________________________________________________    Imidazolidinyl Fused Heteropyridine Carboxylates                               ##STR359##                                                                   Fused                                                                         Heteropyridine                                                                              R.sub.8   R.sub.1                                                                           R.sub.2                                                                              W mp °C.                            __________________________________________________________________________     ##STR360##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR361##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR362##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR363##   C.sub.2 H.sub.5                                                                         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR364##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O trans 186-191 cis 184-191                 ##STR365##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR366##                                                                                  ##STR367##                                                                             CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR368##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR369##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR370##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR371##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR372##   CH.sub.3  CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR373##   CH.sub.3  C.sub.2 H.sub.5                                                                   C.sub.2 H.sub.5                                                                      O                                           ##STR374##   CH.sub.3  CH.sub.3                                                                          cyclo-C.sub.3 H.sub.5                                                                O                                           ##STR375##   CH.sub.3  (CH.sub.2).sub.4 CH(CH.sub.3)                                                            O                                           ##STR376##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR377##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR378##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR379##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR380##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   O                                           ##STR381##   H         C.sub.2 H.sub.5                                                                   C.sub.2 H.sub.5                                                                      O                                           ##STR382##   H         CH.sub.3                                                                          cyclo-C.sub.3 H.sub.5                                                                O                                           ##STR383##   H         (CH.sub.2).sub.4 CH(CH.sub.3)                                                            O                                           ##STR384##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR385##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR386##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR387##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                           ##STR388##   H         CH.sub.3                                                                          CH(CH.sub.3).sub.2                                                                   S                                          __________________________________________________________________________

EXAMPLE 100

Utilizing the procedures of examples 90 and 91, otherimidazopyrroloheteropyridine-2,5-diones areimidazopyrroloheteropyridine-2-thione-5-ones are prepared and are listedin Table X.

                                      TABLE X                                     __________________________________________________________________________    Imidazopyrroloheteropyridine-2,5-diones (-2-thione-5-ones)                     ##STR389##                                                                   Fused                                                                         Heteropyridine                                                                              R.sub.1                                                                              R.sub.2   W mp °C.                                __________________________________________________________________________     ##STR390##   CH.sub.3                                                                             CH(CH.sub.3).sub.2                                                                      O                                               ##STR391##   CH.sub.3                                                                             CH(CH.sub.3).sub.2                                                                      O                                               ##STR392##   CH.sub.3                                                                             CH(CH.sub.3).sub.2                                                                      O                                               ##STR393##   CH.sub.3                                                                             CH(CH.sub.3).sub.2                                                                      O                                               ##STR394##   CH.sub.3                                                                             CH(CH.sub.3).sub.2                                                                      O 225-263                                       ##STR395##   CH.sub. 3                                                                            CH(CH.sub.3).sub.2                                                                      S                                               ##STR396##   CH.sub.3                                                                             CH(CH.sub.3).sub.2                                                                      S                                               ##STR397##   CH.sub.3                                                                             CH(CH.sub.3)2                                                                           S                                               ##STR398##   CH.sub.3                                                                             CH(CH.sub.3).sub.2                                                                      S                                               ##STR399##   CH.sub.3                                                                             CH(CH.sub.3).sub.2                                                                      S                                               ##STR400##   CH.sub.3                                                                             cyclo-C.sub.3 H.sub.5                                                                   O                                               ##STR401##   C.sub.2 H.sub.5                                                                      C.sub.2 H.sub.5                                                                         O                                               ##STR402##   CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH(CH.sub.3)                                               O                                              __________________________________________________________________________

EXAMPLE 101 Postemergence Herbicidal Evaluation of Test Compounds

The postemergence herbicidal activity of the compounds of the presentinvention is demonstrated by the following tests, wherein a variety ofmonocotyledonous and dicotyledonous plants are created with testcompounds dispersed in aqueous acetone mixtures. In the tests, seedlingplants are grown in jiffy flats for about two weeks. The test compoundsare dispersed in 50/50 acetone/water mixtures containing 0.5% TWEEN® 20,a polyoxyethylene sorbitan monolaurate surfactant of Atlas ChemicalIndustries, in sufficient quantity to provide the equivalent of about0.016 kg to 10 kg per hectare of active compound when applied to theplants through a spray nozzle operating at 40 psig for a pre-determinedtime. After spraying, the plants are placed on greenhouse benches andare cared for in the usual manner, commensurate with conventionalgreenhouse practices. From four to five weeks after treatment, theseedling plants, are examined and rated according to the rating systemprovided below. The data obtained are recorded in Table XI below.

    ______________________________________                                                           % Difference in Growth                                     Rating System      from the Check                                             ______________________________________                                        0 -  No effect          0                                                     1 -  Possible effect    1-10                                                  2 -  Slight effect     11-25                                                  3 -  Moderate effect   26-40                                                  5 -  Definite injury   41-60                                                  6 -  Herbicidal effect 61-75                                                  7 -  Good herbicidal effect                                                                          76-90                                                  8 -  Approaching complete kill                                                                       91-99                                                  9 -  Complete kill     100                                                    4 -  Abnormal growth, that is, a definite physiological                            malformation but with an overall effect less than a 5                         on the rating scale.                                                     ______________________________________                                    

In most cases the data are for a single test, but in several instances,they are average values obtained from more than one test.

    ______________________________________                                        Plant Species Used                                                            ______________________________________                                        Barnyardgrass    (Echinochloa crusgalli)                                      Green Foxtail    (Setaria viridis)                                            Purple Nutsedge  (Cyperus rotundus L.)                                        Wild Oats        (Avena fatua)                                                Quackgrass       (Agropyron repens)                                           Field Bindweed   (Convolvulus arvensis L.)                                    Cocklebur        (Xanthium pensylvanicum)                                     Morningglory     (Ipomoea purpurea)                                           Ragweed          (Ambrosia artemisiifolia)                                    Velvetleaf       (Abutilon theophrasti)                                       Barley           (Hordeum vulgare)                                            Corn             (Zea mays)                                                   Rice             (Oryza sativa)                                               Soybean          (Glycine max)                                                Sunflower        (Helianthus annus)                                           Wheat            (Triticum aestivum)                                          ______________________________________                                    

                                      TABLE XI                                    __________________________________________________________________________                     Post-Emergence Tests - Rates in kg/ha                                              FOX                         MRN      VEL-                                BARNY                                                                              TAIL                                                                              P NUT                                                                              WILD                                                                              QUACK                                                                              FLD B                                                                              MATRI                                                                              GLRY                                                                              RAG  VET                Compound     RATE                                                                              ARDGR                                                                              SP  SEDGE                                                                              OATS                                                                              GRASS                                                                              INDWD                                                                              CARIA                                                                              SP  WEED LEAF               __________________________________________________________________________    2-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             9.0  9.0 6.0  9.0 9.0  7.0  2.0  9.0 2.0  4.0                oxo-2-imidazolin-2-yl)-1,8-                                                                .500                                                                              9.0  7.0 4.0  8.0 7.0  7.0  0.0  7.0 0.0  2.0                naphthyridine-3-                                                                           .250                                                                              4.0  6.0 1.0  8.0 7.0  4.0  0.0  6.0 0.0  1.0                carboxylic acid                                                                            .125                                                                              2.0  2.0 0.0  6.0 4.0  2.0  0.0  2.0 0.0  0.0                2-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             2.0  2.0 0.0  4.0 0.0  9.0  0.0  0.0 0.0  2.0                oxo-2-imidazolin-2-yl)-1,6-                                                                .500     2.0 0.0  2.0 0.0  9.0  0.0  0.0 0.0  2.0                naphthyridine-3-                                                                           .250                                                                              2.0  2.0 0.0  1.0 0.0  6.0  0.0  0.0 0.0  2.0                carboxylic acid                                                                            .125                                                                              2.0  1.0 0.0  1.0 0.0  2.0  0.0  0.0 0.0  1.0                2-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             8.0  9.0 0.0  9.0 6.0  8.0  0.0  7.0 0.0  2.0                oxo-2-imidazolin-2-yl)-1,8-                                                                .500                                                                              8.0  9.0 0.0  6.0      6.0  0.0  4.0 0.0  2.0                naphthyridine-3-carboxy-                                                                   .250                                                                              4.0  8.0 0.0  2.0 0.0  4.0  0.0  2.0 0.0  0.0                lic acid, 8-oxide                                                                          .125                                                                              2.0  4.0 0.0  0.0 0.0  2.0  0.0  0.0 0.0  0.0                6-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             9.0  9.0 4.0  8.0 7.0  6.0  7.0  4.0 9.0  7.0                oxo-2-imidazolin-2-yl)-3-                                                                  .500                                                                              2.0  8.0 2.0  4.0 2.0  4.0  2.0  1.0 7.0  4.0                methyl-isoxazolo[5,4-b]                                                                    .250                                                                              0.0  4.0 0.0  0.0 0.0  0.0  0.0  0.0 0.0  0.0                pyridine-5-carboxylic acid                                                    5-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             9.0  9.0 7.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                oxo-2-imidazolin-2-yl)-1-                                                                  .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                methoxy-1H-pyrrolo[3,2-b]                                                                  .250                                                                              9.0  9.0 7.0  9.0 9.0  9.0  9.0  9.0 8.0  9.0                pyridine-6-carboxylic acid                                                                 .125                                                                              9.0  9.0 7.0  9.0 9.0  9.0  9.0  9.0 6.0  9.0                5-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             5.0  9.0 8.0  9.0 4.0       3.0  4.0 4.0  8.0                oxo-2-imidazolin-2-yl)-2-                                                                  .500                                                                              2.0  7.0 3.0  8.0 0.0  3.0  3.0  2.0 4.0  7.0                methyloxazolo[5,4-b]                                                                       .250                                                                              1.0      1.0  6.0 0.0  1.0  0.0  2.0 2.0  4.0                pyridine-6-carboxylic acid                                                                 .125                                                                              0.0  6.0 0.0  1.0 0.0  0.0  0.0  1.0 0.0  2.0                7,8-Dihydro-2-(4-isopropyl-                                                                8.000                                                                             9.0      9.0  9.0 9.0  9.0       8.0 9.0  9.0                4-methyl-5-oxo-2-imidazol-                                                                 1.000                                                                             9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                in-2-yl)-5H-pyrano[4,3-b]                                                                  .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                pyridine-3-carboxylic acid                                                                 .250                                                                              9.0  9.0 9.0  9.0 9.0  9.0  2.0  9.0 9.0  9.0                             .125                                                                              9.0  9.0 9.0  9.0 9.0  9.0  4.0  9.0 9.0  9.0                1-(Allyloxy)-5-(4-                                                                         1.000                                                                             9.0  9.0 4.0  9.0 8.0  9.0  9.0  9.0 9.0  9.0                isopropyl-4-methyl-5-oxo-                                                                  .500                                                                              9.0  9.0 4.0  9.0 7.0  9.0  9.0  9.0 8.0  9.0                2-imidazolin-2-yl)-1H-                                                                     .250                                                                              8.0  9.0 3.0  9.0 7.0  9.0  8.0  8.0 8.0  9.0                pyrrolo[3,2-b]pyridine-                                                                    .125                                                                              7.0  8.0 3.0  9.0 6.0  8.0  7.0  6.0 7.0  9.0                6-carboxylic acid                                                             Methyl 7,8-dihydro-2-(4-                                                                   1.000                                                                             9.0  4.0 6.0  9.0 9.0  8.0  0.0  7.0 5.0  2.0                isopropyl-4-methyl-5-oxo-                                                                  .500                                                                              8.0  4.0 2.0  9.0 7.0  7.0  0.0  4.0 2.0  1.0                2-imidazolin-2-yl)-5H-                                                                     .250                                                                              3.0  2.0 2.0  8.5 2.0  7.0  0.0  3.0 0.0  0.0                pyrano-[4,3-b]pyridine-                                                                    .125                                                                              2.0  1.0 0.0  7.5 0.0  6.0  0.0  0.0 0.0  0.0                3-carboxylate                                                                 Furfuryl 7,8-dihydro-2-(4-                                                                 1.000                                                                             9.0  9.0 7.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                isopropyl-4-methyl-5-oxo-                                                                  .500                                                                              9.0  9.0 7.0  9.0 9.0  9.0  6.0  9.0 8.0  7.0                2-imidazolin-2-yl)-5H-                                                                     .250                                                                              9.0  9.0 6.0  9.0 9.0  9.0  7.0  9.0 8.0  7.0                pyrano-[4,3-b]pyridine-                                                                    .125                                                                              9.0  9.0 5.0  9.0 9.0  9.0  0.0  7.0 6.0  3.0                3-carboxylate                                                                 6-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             4.0  0.0 2.0  9.0 9.0  9.0  0.0  7.0 7.0  2.0                oxo-2-imidazolin-2-yl)-3-                                                                  .500                                                                              2.0  0.0 2.0  8.0 6.0  8.0  0.0  5.0 2.0  1.0                methoxy-1-methyl-1H-                                                                       .250                                                                              1.0  0.0 1.0  8.0 2.0  2.0  0.0  4.0 1.0  0.0                pyrrolo[2,3-b]pyridine-                                                                    .125                                                                              0.0  0.0 0.0  8.0 0.0  0.0  0.0  0.0 2.0  0.0                5-carboxylic acid                                                             2,3-Dihydro-6-(4-isopropyl-                                                                1.000                                                                             9.0  9.0 9.0  9.0 6.0  9.0  9.0  9.0 6.0  8.0                4-methyl-5-oxo-2-imidazol-                                                                 .500                                                                              9.0  9.0 8.0  9.0 6.0  7.0  9.0  9.0 6.0  6.0                in-2-yl)-1-methyl-1H-                                                                      .250                                                                              9.0  9.0 7.0  9.0 8.0  7.0  8.0  9.0 5.0  4.0                pyrrolo[2,3-b]-                                                                            .125                                                                              9.0  9.0 7.0  9.0 7.0  7.0  2.0  7.0 1.0  0.0                pyridine-5-carboxylic acid                                                    7,8-Dihydro-2-(4-isopropyl-                                                                1.000                                                                             9.0  9.0 3.0  9.0 4.0  6.0  5.0  8.0 0.0  3.0                4-methyl-5-oxo-2-imidazol-                                                                 .500                                                                              3.0  4.0 3.0  6.0 2.0  4.0       6.0 0.0  1.0                in-2-yl)-5H-thiopyrano[4,                                                                  .250                                                                              0.0  2.0 2.0  5.0 1.0  1.0  2.0  5.0 0.0  1.0                3-b]pyridine-3-                                                                            .125                                                                              0.0  0.0 1.0  3.0 0.0  1.0  1.0  2.0 0.0  0.0                carboxylic acid                                                               5-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             9.0  9.0 7.0  9.0 8.0  9.0  9.0  9.0 8.0  9.0                oxo-2-imidazolin-2-yl)-1-                                                                  .500                                                                              9.0  9.0 9.0  9.0 8.0  8.0  9.0  8.0 8.0  9.0                methyl-1H-pyrrolo[3,2-b]                                                                   .250                                                                              9.0  9.0 8.0  9.0 8.0  8.0  9.0  8.0 9.0  9.0                pyridine-6-carboxylic acid                                                                 .125                                                                              9.0  9.0 8.0  9.0 8.0  7.0  8.0  8.0 2.0  9.0                3,4-Dihydro-7-(4-isopropyl-                                                                1.000                                                                             9.0  9.0 9.0  9.0 9.0  7.0       8.0 6.0  9.0                4-methyl-5-oxo-2-imi-                                                                      .500                                                                              9.0  9.0 6.0  9.0 8.0  7.0  5.0  7.0 3.0  8.0                dazolin-2-yl)-2H-thio-                                                                     .250                                                                              9.0  6.0 4.0  9.0 8.0  7.0  2.0  7.0 1.0  8.0                pyrano[2,3-b]pyridine-6-                                                                   .125                                                                              9.0  4.0 2.0  8.0 7.0  6.0  0.0  5.0 0.0  2.0                carboxylic acid                                                               3,4-Dihydro-7-(4-isopropyl-                                                                1.000                                                                             9.0  9.0 9.0  9.0 9.0  8.0  8.0  9.0 9.0  9.0                4-methyl-5-oxo-2-imidazol-                                                                 .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  5.0  9.0 8.0  9.0                in-2-yl)-2H-pyrano[2,3-b]                                                                  .250                                                                              9.0  9.0 9.0  9.0 8.0  9.0  5.0  8.0 6.0  9.0                pyridine-6-carboxylic acid                                                                 .125                                                                              9.0  9.0 9.0  9.0 7.0  8.0  5.0  7.0 2.0  9.0                6-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             9.0  9.0 9.0  9.0 9.0  9.0       8.0 9.0  6.0                oxo-2-imidazolin-2-yl)-1-                                                                  .500                                                                              9.0  9.0 7.0  9.0 9.0  7.0       8.0 9.0  6.0                methyl-1H-pyrrolo[2,3-b]                                                                   .250                                                                              9.0  9.0 8.0  9.0 9.0  7.0       5.0 6.0  5.0                pyridine-5-carboxylic acid                                                                 .125                                                                              9.0  9.0 8.0  9.0 9.0  7.0  2.0  8.0 5.0  3.0                5-(4-Isopropyl-4-methyl-5-                                                                 1.000                                                                             9.0  9.0 7.0  9.0 8.0  9.0  9.0  9.0 8.0  9.0                oxo-2-imidazolin-2-yl)-1-                                                                  .500                                                                              9.0  9.0 7.0  9.0 9.0  9.0  7.0  9.0 8.0  9.0                methoxy-2-methyl-1H-                                                                       .250                                                                              9.0  9.0 5.0  9.0 9.0  9.0       9.0 7.0  9.0                pyrrolo[3,2-b]pyridine-6-                                                                  .125                                                                              9.0  9.0 4.0  9.0 6.0  8.0       9.0 6.0  9.0                carboxylic acid                                                               __________________________________________________________________________

EXAMPLE 102 Preemergence Herbicidal Evaluation of Test Compounds

The preemergence herbicidal activity of the compounds of the presentinvention is exemplified by the following tests in which the seeds of avariety of monocotyledonous and dicotyledonous plants are separatelymixed with potting soil and planted on top of approximately one inch ofsoil in separate pint cups. After planting, the cups are sprayed withthe selected aqueous acetone solution containing test compound insufficient quantity to provide the equivalent of about 0.016 to 10 kgper hectare of test compound per cup. The treated cups are then placedon greenhouse benches, watered and cared for in accordance withconventional greenhouse procedures. From four to five weeks aftertreatment, the tests are terminated and each cup is examined and ratedaccording to the rating system set forth above. The herbicidalproficiency of the active ingredients of the present invention isevident from the test results which are recorded in Table XII below.Where more than one test is involved for a given compound, the data areaveraged.

                                      TABLE XII                                   __________________________________________________________________________                     Pre-Emergence Tests - Rates in kg/ha                                               FOX                         MRN      VEL-                                BARNY                                                                              TAIL                                                                              P NUT                                                                              WILD                                                                              QUACK                                                                              FLD B                                                                              MATRI                                                                              GLRY                                                                              RAG  VET                Compound     RATE                                                                              ARDGR                                                                              SP  SEDGE                                                                              OATS                                                                              GRASS                                                                              INDWD                                                                              CARIA                                                                              SP  WEED LEAF               __________________________________________________________________________    6-(4-Isopropyl-4-methyl-5-                                                                 .500                                                                              4.0  9.0 9.0  8.0 9.0  9.0  9.0  8.0 8.0  8.0                oxo-2-imidazolin-2-yl)-                                                                    .250                                                                              2.0  6.0 6.0  4.0 6.0  6.0  8.0      6.0  8.0                3-methyl-isoxazolo[5,                                                                      .125                                                                              0.0  2.0 4.0  0.0 0.0  1.0  0.0  3.0 0.0  6.0                4-b]pyridine-5-                                                               carboxylic acid                                                               6-(4-Isopropyl-4-methyl-5-                                                                 .500                                                                              7.0  7.0 7.0  7.0 9.0  9.0  0.0  3.0 0.0  5.0                oxo-2-imidazolin-2-yl)-1H-                                                                 .250                                                                              5.0  4.0 5.0  5.0 7.0  9.0  0.0  1.0 0.0  2.0                pyrazolo[3,4-b]pyridine-                                                                   .125                                                                              1.0  1.0 3.0  3.0 3.0  9.0  0.0  0.0 0.0  1.0                5-carboxylic acid                                                             6-(4-Isopropyl-4-methyl-5-                                                                 .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  2.0  9.0 7.0  4.0                oxo-2-imidazolin-2-yl)-1-                                                                  .250                                                                              8.0  9.0 9.0  8.0 9.0  9.0  0.0  9.0 3.0  4.0                methyl-1H-pyrazolo[3,4-b]-                                                                 .125                                                                              5.0  9.0 9.0  9.0 9.0  9.0  0.0  9.0 0.0  4.0                pyridine-5-carboxylic acid                                                    6-(4-Isopropyl-4-methyl-5-                                                                 .500                                                                              0.0  4.0 9.0  0.0 9.0  9.0  4.0  8.0 6.0  6.0                oxo-2-imidazolin-2-yl)-2-                                                                  .250                                                                              0.0  0.0 9.0  0.0 9.0  7.0  1.0  4.0 2.0  5.0                methyl-2H-pyrazolo[3,4-b]-                                                                 .125                                                                              0.0  0.0 9.0  0.0 9.0  4.0  0.0  0.0 1.0  2.0                pyridine-5-carboxylic acid                                                    5-(4-Isopropyl-4-methyl-5-                                                                 .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                oxo-2-imidazolin-2-yl)-                                                                    .250                                                                              9.0  9.0 9.0  9.0 9.0  9.0  8.0  9.0 9.0  9.0                1-methoxy-1H-pyrrolo[3,                                                                    .125                                                                              9.0  9.0 9.0  9.0 9.0  9.0  8.0  9.0 8.0  9.0                2-b]pyridine-6-                                                               carboxylic acid                                                               7,8-Dihydro-2-(4-isopropyl-                                                                8.000                                                                             9.0      9.0  9.0 9.0  9.0       8.0 9.0  9.0                4-methyl-5-oxo-2-imidazol-                                                                 .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                in-2-yl)-5H-pyrano[4,                                                                      .250                                                                              9.0  9.0 9.0  9.0 9.0  9.0  7.0  9.0 9.0  9.0                3-b]pyridine-3-                                                                            .125                                                                              9.0  8.0 9.0  9.0 9.0  9.0  4.0  9.0 9.0  8.0                carboxylic acid                                                               1-(Allyloxy)-5-(4-                                                                         .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                isopropyl-4-methyl-5-                                                                      .250                                                                              9.0  9.0 8.0  9.0 9.0  9.0  9.0  9.0 8.0  9.0                oxo-2-imidazolin-2-yl)-                                                                    .125                                                                              9.0  9.0 9.0  9.0 9.0  8.0  9.0  9.0 8.0  9.0                1H-pyrrolo[3,2-b]-                                                            pyridine-6-                                                                   carboxylic acid                                                               Methyl 7,8-dihydro-2-(4-                                                                   .500                                                                              6.0  9.0 9.0  9.0 9.0  9.0  5.0  8.0 6.0  7.0                isopropyl-4-methyl-5-oxo-                                                                  .250                                                                              2.0  7.0 7.0  9.0 9.0  8.0  1.0  4.0 2.0  5.0                2-imidazolin-2-yl)-5H-                                                                     .125                                                                              0.0  6.0 6.0  9.0 3.0  8.0  0.0  1.0 0.0  2.0                pyrano[4,3-b]pyridine-                                                        3-carboxylate                                                                 Furfuryl 7,8-dihydro-2-(4-                                                                 .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  8.0                isopropyl-4-methyl-5-oxo-                                                                  .250                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                2-imidazolin-2-yl)-5H-                                                                     .125                                                                              4.0  9.0 9.0  9.0 9.0  9.0  4.0  8.0 5.0  7.0                pyrano[4,3-b]pyridine-                                                        3-carboxylate                                                                 6-(4-isopropyl-4-methyl-5-                                                                 .500                                                                              4.0  0.0 6.0  9.0 8.0  7.0  2.0  8.0 8.0  7.0                oxo-2-imidazolin-2-yl)-3-                                                                  .250                                                                              1.0  0.0 2.0  4.0 6.0  4.0       8.0 2.0  2.0                methoxy-1-methyl-1H-                                                          pyrrolo[2,3-b]pyridine-                                                       5-carboxylic acid                                                             2,3-Dihydro-6-(4-isopropyl-                                                                .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  7.0  9.0 7.0  7.0                4-methyl-5-oxo-2-                                                                          .250                                                                              8.0  9.0 9.0  9.0 9.0  9.0  7.0  9.0 7.0  7.0                imidazolin-2-yl)-1-methyl-                                                                 .125                                                                              6.0  9.0 9.0  9.0 9.0  4.0  6.0  8.0 4.0  6.0                1H-pyrrolo[2,3-b]                                                             pyridine-5-carboxylic acid                                                    3-(m-chlorophenyl)-7-(4-                                                                   .500                                                                              2.0  6.0 0.0  8.5 1.0  0.0  0.0  0.0 0.0  1.0                isopropyl-4-methyl-5-oxo-                                                                  .250                                                                              0.5  2.0 0.0  8.0 1.0  0.0  0.0  0.0 0.0  1.0                2-imidazolin-2-yl)-4-                                                                      .125                                                                              0.0  0.0 0.0  7.5 0.5  0.0  0.0  0.0 0.0  0.5                methyl-2-oxo-2H-pyrano[2,                                                     3-b]pyridine-6-                                                               carboxylic acid                                                               3-(p-chlorophenyl-7-(4-iso-                                                                4.000                                                                             6.0      0.0  8.0 9.0  0.0       4.0 7.0  6.0                propyl-4-methyl-5-oxo-2-                                                                   .500                                                                              5.0  7.0 0.0  9.0 4.0  0.0  0.0  0.0 2.0  0.0                imidazolin-2-yl)-4-methyl-                                                                 .250                                                                              0.0  1.0 0.0  9.0 1.0  0.0  0.0  0.0 0.0  0.0                2-oxo-2H-pyrano[2,3-b]-                                                                    .125                                                                              0.0  0.0 0.0  8.0 0.0  0.0  0.0  0.0 0.0  0.0                pyridine-6-carboxylic acid                                                    5-(4-isopropyl-4-methyl-5-                                                                 .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  9.0                oxo-2-imidazolin-2-yl)-1-                                                                  .250                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  8.0 9.0  9.0                methyl-1H-pyrrolo[3,2-b]-                                                                  .125                                                                              9.0  9.0 9.0  9.0 9.0  9.0  8.0  4.0 8.0  9.0                pyridine-6-carboxylic acid                                                    3,4-Dihydro-7-(4-isopropyl-                                                                .500                                                                              2.0  4.0 6.0  8.0 6.0  2.0  0.0  5.0 6.0  6.0                4-methyl-5-oxo-2-                                                                          .250                                                                              1.0  0.0 3.0  3.0 2.0  2.0  0.0  2.0 4.0  4.0                imidazolin-2-yl)-2H-                                                                       .125                                                                              0.0  0.0 0.0  1.0 0.0  1.0  0.0  0.0 2.0  2.0                thiopyrano[2,3-b]-                                                            pyridine-6-                                                                   carboxylic acid                                                               3,4-Dihydro-7-(4-isopropyl-                                                                .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  4.0  9.0 8.0  8.0                4-methyl-5-oxo-2-                                                                          .250                                                                              9.0  9.0 9.0  9.0 9.0  9.0  4.0  8.0 6.0  7.0                imidazolin-2-yl)-2H-                                                                       .125                                                                              4.0  9.0 8.0  9.0 9.0  8.0  2.0  6.0 2.0  5.0                pyrano[2,3-b]pyri-                                                            dine-6-carboxylic acid                                                        6-(4-Isopropyl-4-methyl-5-                                                                 .500                                                                              9.0  9.0 9.0  9.0 9.0  9.0  9.0  9.0 9.0  8.0                oxo-2-imidazolin-2-yl)-1-                                                                  .250                                                                              9.0  9.0 7.0  9.0 9.0  9.0  6.0  9.0 9.0  8.0                methyl-1H-pyrrolo[2,3-b]-                                                                  .125                                                                              7.0  9.0 8.0  9.0 9.0  7.0  2.0  9.0 9.0  6.0                pyridine-5-carboxylic acid                                                    5-(4-Isopropyl-4-methyl-5-                                                                 .500                                                                              9.0  9.0 8.0  9.0 9.0  9.0  8.0  9.0 8.0  9.0                oxo-2-imidazolin-2-yl)-1-                                                                  .250                                                                              9.0  9.0 8.0  9.0 9.0  9.0  8.0  9.0 6.0  9.0                methoxy-2-methyl-1H-                                                                       .125                                                                              9.0  9.0 7.0  9.0 9.0  7.0  8.0  9.0 6.0  9.0                pyrrolo-[3,2-b]pyridine-                                                      6-carboxylic acid                                                             2-(4-Isopropyl-4-methyl-                                                                   .500                                                                              0.0  2.0 9.0  6.0 9.0  9.0  0.0  8.0      6.0                5-oxo-2-imidazolin-2-yl)-                                                                  .250                                                                              0.0  0.0 9.0  4.0 9.0  9.0  0.0  8.0 0.0  3.0                1,8-naphthyridine-3-                                                                       .125                                                                              0.0  0.0 6.0  2.0 8.0  4.0  0.0  0.0 0.0  2.0                carboxylic acid                                                               __________________________________________________________________________

What is claimed is:
 1. (2-Imidazolin-2-yl) fused heteropyridinecompounds having the structure ##STR403## wherein A is COOR₈, CHO, CH₂OH, COCH₂ OH, CONH₂, CH₂ CH₂ OH, CONHOH or ##STR404## R_(C) and R_(D)are each hydrogen or C₁ -C₄ alkyl; R_(B) is hydrogen, C₁ -C₄ alkyl whichmay be interrupted by O or S, or is optionally substituted with C₁ -C₄alkoxy, halogen, hydroxy, C₃ -C₆ cycloalkyl, benzyloxy, furyl, phenyl,furfuryl, halophenyl, C₁ -C₄ alkylphenyl, C₁ -C₄ alkoxyphenyl,nitrophenyl, carboxyl, C₁ -C₄ alkoxy carbonyl, cyano or C₁ -C₄trialkylammonium; C₃ -C₆ alkenyl, optionally substituted with one or twoC₁ -C₃ alkoxy, phenyl or halogen groups; C₃ -C₆ cycloalkyl, optionallysubstituted with one or two C₁ -C₃ alkyl groups; C₃ -C₁₀ alkynyl,optionally substituted with phenyl, halogen, C₁ -C₄ alkoxy; or a cationselected from the group consisting of alkali metals, alkaline earthmetals, manganese, copper, iron, ammonium and organic ammonium;B is H,COR₉ or SO₂ R₁₀, R₉ is C₁ -C₁₁ alkyl, chloromethyl, C₁ -C₄ alkoxyl orphenyl optionally substituted with one chloro, one nitro, one methyl, orone methoxy group; R₁₀ is C₁ -C₅ alkyl, phenyl, or phenyl substitutedwith one methyl, halogen, nitro or C₁ -C₄ alkoxy; R₁ is C₁ -C₄ alkyl; R₂is C₁ -C₄ alkyl or C₃ -C₆ cycloalkyl;and when taken together with thecarbon to which they are attached, R₁ and R₂ may represent C₃ -C₆cycloalkyl, optionally substituted with methyl; - - - represents asingle or double bond; W is O or S; ₁. X₂, X₃ and X₄ are any combinationof CR₄, CR₅ R₆, N or NR₃ and are the same or different, with the provisothat at least two of X₁, X₂, and X₄ must be N or NR₃, one of X₁, X₂, andX₄ must be CR₄ or CR₅ R₆, and one of X₁, X₂ and X₄ must be O or S;Y₁ andY₂ are N or CR₄ with the proviso that one of Y₁ and Y₂ must be N and theother must be CR₄ ; Z₁ is O or S; R₃ is C₁ -C₄ alkyl, which may beoptionally substituted with phenyl or one or more halogens; C₃ -C₆alkenyl, optionally substituted with phenyl or one or more halogens; C₃-C₆ alkynyl, optionally substituted with phenyl or halogen; C₁ -C₄alkoxy, optionally substituted with phenyl or one or more halogens; C₃-C₆ alkenyloxy optionally substituted with phenyl or one or morehalogens; C₃ -C₆ alkynyloxy optionally substituted with halogen orphenyl; or C₂ -C₆ alkanoyloxy, optionally substituted with halogen orphenyl; R₄ is hydrogen, halogen, C₁ -C₆ alkyl; C₁ -C₄ alkoxy; C₂ -C₆alkanoyloxy; C₁ -C₄ alkylthio; phenoxy; C₁ -C₄ haloalkyl, C₁ -C₄haloalkoxy; nitro, C₁ -C₄ alkoxycarbonyl; C₁ -C₄ dialkylamino; C₁ -C₄alkylsulfonyl or phenyl, optionally substituted with one or two C₁ -C₄alkyl, C₁ -C₄ alkoxy, halogen or C₁ -C₄ haloalkyl; R₅ and R₆ are eachhydrogen, C₁ -C₄ alkyl; C₁ -C₄ alkoxy, C₁ -C₄ haloalkoxy; nitro, C₁ -C₄alkylsulfonyl or phenyl optionally substituted with one or two C₁ -C₄alkyl, C₁ -C₄ alkoxy, halogen or C₁ -C₄ haloalkyl; or any combination ofthese groups except when R₅ and R₆ are the same group, they are eitherboth hydrogen or both C₁ -C₄ alkyl; and when taken together, R₅ and R₆may form a ring in which R₅ R₆ are represented by the structure--(CH₂)_(n) -- where n is an integer of 4 or 5, or when taken together,R₅ and R₆ may form a group ═O or ═NR₇ wherein R₇ is phenyl, C₁ -C₄alkyl, C₁ -C₄ alkoxy, C₁ -C₄ alkylamino; R₃, R₄, R₅ and R₆, when presenton adjacent positions may, along with the atoms to which they areattached, form a ring and such R₃ -R₆ pairs can be represented by thestructure --(CH₂)_(m) -- or --(CH)_(m) -- where m is an integer of 3 or4;with the provisos that - - - represents a single bond between: X₁ andX₂ when either X₁ or X₂ is S, O, NR₃ or CR₅ R₆ ; X₂ and X₄ when eitherX₂ or X₄ is O, S, NR₃ or CR₅ R₆ ; and when B is COR₉ or SO₂ R₁₀ and R₈is hydrogen, then - - - represents an aromatic bond, R₃ is C₁ -C₄ alkyl,and R₄, may not be halogen.
 2. The compound according to claim 1 whereinthe structural formulae is structure II or IV.
 3. The compound accordingto claim 1 wherein the structural formulae is structure II.
 4. Thecompound according to claim 1,wherein R₁ is methyl or ethyl, R₂ isethyl, propyl, isopropyl and when R₁ and R₂ are taken together, theyrepresent a cyclohexyl ring, optionally substituted with methyl; R₃ isC₁ -C₃ alkyl, C₁ -C₄ alkoxy, allyloxy, CF₃ O--, CF₂ HO-- or CF₃ ; A isCOOR₈ wherein R₈ is hydrogen, C₁ -C₄ alkyl, which may be interrupted byO or S, or is optionally substituted with C₁ -C₄ alkoxy, halogen,hydroxy, C₃ -C₆ cycloalkyl, benzyloxy, furyl, phenyl, furfuryl,halophenyl, C₁ -C₄ alkylphenyl, C₁ -C₄ alkoxyphenyl, nitrophenyl,carboxyl, C₁ -C₄ alkoxycarbonyl, cyano or C₁ -C₄ trialkylammonium; C₃-C₆ alkenyl, optionally substituted with one or two C₁ -C₃ alkoxy,phenyl, halogen, C₃ -C₆ cycloalkyl, optionally substituted with one ortwo C₁ -C₃ alkyl groups; C₃ -C₁₀ alkynyl, optionally substituted withphenyl, halogen, C₁ -C₄ alkoxy, or a cation selected from the groupconsisting of alkali metals, alkaline earth metals, manganese, copper,iron, ammonium and organic ammonium.
 5. The compound according to claim4, whereinB is H, benzoyl, acetyl, methanesulfonyl or p-toluenesulfonyl;R₁ is methyl and R₂ is isopropyl; R₃ is methyl, ethyl, methoxy, ethoxyand allyloxy; R₄, R₅ and R₆ are each methyl, ethyl, hydrogen, methoxyand ethoxy, or R₅ R₆, when taken together are ═O; and W is O; R₈ ishydrogen, methyl, ethyl, propargyl, phenyl substituted alkyl, or asodium, calcium, lithium, potassium, magnesium, ammonium, or mono-, di-,tri or tetraalkylammonium cation.
 6. A method for the control ofmonoeotyledonous and dicotyledonous annual, perennial and aquatic plantspecies comprising: applying to the foliage of said plants or to soil orwater containing seeds or other propagating organs thereof, aherbicidally effective amount of compounds having structures ##STR405##wherein A is COOR₈, CHO, CH₂ OH, COCH₂ OH, CONH₂, CH₂ CH₂ OH, CONHOH or##STR406## R_(C) and R_(D) are each hydrogen or C₁ -C₄ alkyl; R₈ ishydrogen, C₁ -C₄ alkyl which may be interrupted by O or S, or isoptionally substituted with C₁ -C₄ alkoxy, halogen, hydroxy, C₃ -C₆cycloalkyl, benzyloxy, furyl, phenyl, furfuryl, halophenyl, C₁ -C₄alkylphenyl, C₁ -C₄ alkoxyphenyl, nitrophenyl, carboxyl, C₁ -C₄ alkoxycarbonyl, cyano or C₁ -C₄ trialkylammonium; C₃ -C₆ alkenyl, optionallysubstituted with one or two C₁ -C₃ alkoxy, phenyl or halogen groups;. C₃-C₆ cycloalkyl, optionally substituted with one or two C₁ -C₃ alkylgroups; C₃ -C₁₀ alkynyl, optionally substituted with phenyl, halogen, C₁-C₄ alkoxy; or a cation selected from the group consisting of alkalimetals, alkaline earth metals, manganese, copper, iron, ammonium andorganic ammonium;B is H, COR₉ or SO₂ R₁₀, R₉ is C₁ -C₁₁ alkyl,chloromethyl, C₁ -C₄ alkoxyl or phenyl optionally substituted with onechloro, one nitro, one methyl, or one methoxy group; R₁₀ is C₁ -C₅alkyl, phenyl, or phenyl substituted with one methyl, halogen, nitro orC₁ -C₄ alkoxy; R₁ is C₁ -C₄ alkyl; R₂ is C₁ -C₄ alkyl or C₃ -C₆cycloalkyl;and when taken together with the carbon to which they areattached, R₁ and R₂ may represent C₃ -C₆ cycloalkyl, optionallysubstituted with methyl; - - - represents a single or double bond; W isO or S; X₁, X₂, X₃ and X₄ are any combination of CR₄, CR₅ R₆, O, S, N orNR₃ and are the same or different, with the proviso that at least two ofX₁, X₂, and X₄ must be N or NR₃, one of X₁, X₂, and X₄ must be CR₄ orCR₅ R₆, and one of X₁, X₂ and X₄ must be O or S; Y₁ and Y₂ are N or CR₄with the provicso that one of Y₁ and Y₂ must be N and the other must beCR₄ ; Z₁ is O or S; R₃ is C₁ -C₄ alkyl, which may be optionallysubstituted with phenyl or one or more halogens; C₃ -C₆ alkenyl,optionally substituted with phenyl or one or more halogens; C₃ -C₆alkynyl, optionally substituted with phenyl or halogen; C₁ -C₄ alkoxy,optionally substituted with phenyl or one or more halogens; C₃ -C₆alkenyloxy optionally substituted with phenyl or one or more halogens;C₃ -C₆ alkynyloxy optionally substituted with halogen or phenyl; or C₂-C₆ alkanoyloxy, optionally substituted with halogen or phenyl; R₄ ishydrogen, halogen, C₁ -C₆ alkyl; C₁ -C₄ alkoxy; C₂ -C₆ alkanoyloxy; C₁-C₄ alkylthio; phenoxy; C₁ -C₄ haloalkyl, C₁ -C₄ haloalkoxy; nitro, C₁-C₄ alkoxycarbonyl; C₁ -C₄ dialkylamino; C₁ -C₄ alkylsulfonyl or phenyl,optionally substituted with one or two C₁ -C₄ alkyl, C₁ -C₄ alkoxy,halogen or C₁ -C₄ haloalkyl; R₅ and R₆ are each hydrogen, C₁ -C₄ alkyl;C₁ -C₄ alkoxy, C₁ -C₄ haloalkoxy; nitro, C₁ -C₄ alkylsulfonyl or phenyloptionally substituted with one or two C₁ -C₄ alkyl, C₁ -C₄ alkoxy,halogen or C₁ -C₄ haloalkyl; or any combination of these groups exceptwhen R₅ and R₆ are the same group, they are either both hydrogen or bothC₁ -C₄ alkyl; and when taken together, R₅ and R₆ may form a ring inwhich R₅ R₆ are represented by the structure --(CH₂)_(n--) where n is aninteger of 4 or 5, or when taken together, R₅ and R₆ may form a group ═Oor ═NR₇ wherein R₇ is phenyl, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₁ -C₄alkylamino; R₃, R₄, R₅ and R₆, when present on adjacent positions may,along with the atoms to which they are attached, form a ring and such R₃-R₆ pairs can be represented by the structure --(CH₂)_(m) -- or--(CH)_(m) -- where m is an integer of 3 or 4;with the provisosthat - - - represents a single bond between; X₁ and X₂ when either X₁ orX₂ is S, O, NR₃ or CR₅ R₆ ; X₂ and X₃ when either X₂ or X₄ is O, S, NR₃or CR₅ R₆ ; andand when B is COR₉ or SO₂ R₁₀ and R₈ is hydrogen,then - - - represents an aromatic bond, R₃ is C₁ -C₄ alkyl, and R₄, maynot be halogen.
 7. The method according to claim 6 wherein one of thefused heteropyridine compound has structural formula II or IV.
 8. Themethod according to claim 6 wherein the structural formulae is structureII.
 9. The method according to claim 6, whereinR₁ is methyl or ethyl, R₂is ethyl, propyl, isopropyl and when R₁ and R₂ are taken together, theyrepresent a cyclohexyl ring, optionally substituted with methyl; R₃ isC₁ -C₃ alkyl, C₁ -C₄ alkoxy, allyloxy, CF₃ O--, CF₂ HO-- or CF₃ ; A isCOOR₈ wherein R₈ is hydrogen, C₁ -C₄ alkyl, which may be interrupted byO or S, or is optionally substituted with C₁ -C₄ alkoxy, halogen,hydroxy, C₃ -C₆ cycloalkyl, benzyloxy, furyl, phenyl, furfuryl,halophenyl, C₁ -C₄ alkylphenyl, C₁ -C₄ alkoxyphenyl, nitrophenyl,carboxyl, C₁ -C₄ alkoxycarbonyl, cyano or C₁ -C₄ trialkylammonium; C₃-C₆ alkenyl, optionally substituted with one or two C₁ -C₃ alkoxy,phenyl, halogen, C₃ -C₆ cycloalkyl, optionally substituted with one ortwo C₁ -C₃ alkyl groups; C₃ -C₁₀ alkynyl, optionally substituted withphenyl, halogen, C₁ -C₄ alkoxy, or a cation selected from the groupconsisting of alkali metals, alkaline earth metals, manganese, copper,iron, ammonium and organic ammonium.
 10. A method according to claim 6,whereinB is H, benzoyl, acetyl, methanesulfonyl or p-toluenesulfonyl; R₁is methyl and R₂ is isopropyl; R₃ is methyl, ethyl, methoxy, ethoxy andallyloxy; R₄, R₅ and R₆ are each methyl, ethyl, hydrogen, metboxy andethoxy, or R₅ R₆, when taken together are ═O; and W is O; R₈ ishydrogen, methyl, ethyl, propargyl, phenyl substituted alkyl, or asodium, calcium, lithium, potassium, magnesium, ammonium, or mono-, di-,tri or tetraalkylammonium cation.